Confirmation of visual field abnormalities in the Ocular Hypertension Treatment Study. Ocular Hypertension Treatment Study Group.

OBJECTIVE: To determine the frequency with which visual field abnormalities observed on follow-up visual fields for patients in the Ocular Hypertension Treatment Study were confirmed on retest. METHODS: Between April 1, 1994, and March 1, 1999, 21,603 visual fields were obtained from 1637 patients in the Ocular Hypertension Treatment Study. When follow-up visual fields are outside the normal limits on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation (P<.05), or both, subsequent follow-up visual fields are monitored to confirm the abnormality. Abnormalities are confirmed if they are again abnormal on the Glaucoma Hemifield Test, the Corrected Pattern Standard Deviation, or both; if the defect is not artifactual; and if the same index and location are involved. Reliability criteria used by the study consisted of a limit of 33% for false positives, false negatives, and fixation losses. RESULTS: Of the 21,603 regular follow-up visual fields, 1006 were follow-up retests performed because of an abnormality (n = 748) or unreliability (n = 258). We found that 703 (94%) of the 748 visual fields were abnormal and reliable, and 45 (6%) were abnormal and unreliable. On retesting, abnormalities were not confirmed for 604 (85.9%) of the 703 originally abnormal and reliable visual fields. CONCLUSIONS: Most visual field abnormalities in patients in the Ocular Hypertension Treatment Study were not verified on retest. Confirmation of visual field abnormalities is essential for distinguishing reproducible visual field loss from long-term variability. Arch Ophthalmol. 2000;118:1187-1194

Predicting binocular visual field sensitivity from monocular visual field results.

PURPOSE: To compare methods of predicting binocular visual field sensitivity of patients with glaucoma from monocular visual field data. METHODS: Monocular and binocular visual fields were obtained for 111 patients with varying degrees of glaucomatous damage in one or both eyes, using the Humphrey 30-2 full-threshold procedure. Four binocular sensitivity prediction models were evaluated: BEST EYE, predictions based on individual values for the most sensitive eye, defined by mean deviation (MD); AVERAGE EYE, predictions based on the average sensitivity between eyes at each visual field location; BEST LOCATION, predictions based on the highest sensitivity between eyes at each visual field location; and BINOCUIAR SUMMATION, predictions based on binocular summation of sensitivity between eyes at each location. Differences between actual and predicted binocular sensitivities were calculated for each model. RESULTS: The average difference between predicted and actual binocular sensitivities was close to zero for the BINOCULAR SUMMATION and BEST LOCATION models, with 95% of all predictions being within +/-3 dB of actual binocular sensitivities. The best eye (MD) prediction had an average error of 1.5 dB (95% confidence limits [CL], +/-3.7 dB). The average eye prediction was the poorest, with an average error of 3.7 dB (95% CL, +/-4.6 dB). CONCLUSIONS: The BINOCULAR SUMMATION and BEST LOCATION models provided better predictions of binocular visual field sensitivity than the other two models, with a statistically significant difference in performance. The small difference in performance between the BINOCULAR SUMMATION and BEST LOCATION models was not statistically significant. For evaluations of functional visual field influences on task performance, daily activities, and related quality-of-life issues, either the BINOCULAR SUMMATION or BEST LOCATION model provides good estimates of binocular visual field sensitivity.

Frequency doubling technology perimetry for detection of glaucomatous visual field loss.

PURPOSE: To evaluate the ability of frequency doubling technology perimetry to detect early, moderate, and advanced glaucomatous visual field loss. METHODS: In a prospective study, frequency doubling technology perimetry (C-20 full threshold) was performed in the right eye of 254 normal control subjects and 230 patients with early (n = 85), moderate (n = 114), or advanced (n = 31) glaucomatous visual field loss. Previous Humphrey Field Analyzer test results were used to classify glaucomatous visual field loss as early (mean deviation no worse than -6 dB), moderate (mean deviation between -6 and -12 dB) or advanced (mean deviation between -12 and -22 dB). RESULTS: Receiver operating characteristic curves showed 100% sensitivity and specificity (area under the curve, 1.0) for detecting advanced glaucomatous visual field loss, approximately 96% sensitivity and 96% specificity (area under the curve, 0.9751) for detecting moderate glaucomatous visual field loss, and approximately 85% sensitivity and 90% specificity (area under the curve, 0.9261) for early glaucomatous visual field loss. CONCLUSIONS: Frequency doubling technology perimetry demonstrates high sensitivity and specificity for detection of early, moderate, and advanced glaucomatous visual field loss.

Evaluation of CMC and HA solutions for adhesiolysis.

Aqueous hyaluronic acid (HA) and carboxymethylcellulose (CMC) solutions were tested as tissue-protective coatings during lysis of surgical adhesions by blunt dissection or electrocautery in a rat cecal abrasion model. Phosphate-buffered saline (PBS) was used as a tissue coating solution in 200 female Sprague-Dawley rats prior to controlled cecal abrasion with a surgical gauze-tipped rotary abrader (four 1.5-cm-diameter areas; 70 g weight/60 revolutions/130 rpm). One-week after this initial cecal abrasion, rats were operated on again and adhesions were scored and lysed. The rats were randomly assigned to receive experimental tissue coating solutions either before (prelysis; n = 160) or after (postlysis; n = 40) adhesiolysis. Animals with prelysis coatings were further divided into blunt dissection or electrocautery adhesiolysis groups and were tested with 2 mL cecal coating of PBS, 0.4% HA, 0.5% CMC, or 1.0% CMC tissue coating solutions (n = 20/group). Rats treated postlysis received 2 mL cecal coating plus 2 mL intraperitoneal instillation of PBS, 1.8, 1.9, or 2.0% CMC. One week after adhesiolysis, rats were operated on again for final adhesion scoring. Prelysis tissue coating with 0.5 or 1.0% CMC solution appeared to inhibit adhesion reformation after blunt dissection, whereas 0.4% HA was not effective in this model. Solutions applied before electrocautery dissection or after blunt dissection were ineffective.

Temporal modulation perimetry: the effects of aging and eccentricity on sensitivity in normals.

PURPOSE: Temporal modulation perimetry (TMP) is a new test procedure designed to measure sensitivity to sinusoidal flickering stimuli throughout the central 27 degrees visual field. The purpose of this investigation was to determine the effect of age and visual field eccentricity on temporal modulation sensitivity. METHOD: In its present form, TMP is used to determine modulation sensitivity for three temporal frequencies (2, 8, and 16 Hz) at 45 visual field locations. Both eyes of 43 normal observers between 20 and 75 years of age were examined. RESULTS: Our results indicate that sensitivity to all temporal frequencies tested showed a decline with age, particularly in the peripheral visual field. Furthermore, the age-related sensitivity loss was more pronounced for 16 Hz than for 2 or 8 Hz. CONCLUSIONS: These data demonstrate an age-related loss in temporal modulation sensitivity in the peripheral visual field. They also provide a baseline comparison standard for evaluation of clinical patient populations.

Synthesis, properties, and intratumoral evaluation of mitoxantrone-loaded casein microspheres in Lewis lung carcinoma.

Smooth, round, uniform bovine casein microspheres of 1-5 and 10-20 microns size were readily prepared by a steric stabilization technique previously developed in this laboratory for synthesis of albumin microspheres. The avid phagocytic uptake of casein and albumin microspheres was demonstrated with fluorescein-labelled microspheres using a macrophage-like mouse myelomonocytic leukaemia cell line. Post-synthesis loading of 25% mitoxantrone was achieved for casein microspheres containing 20% polyglutamic acid. Preliminary intratumoural chemotherapy experiments with a mouse Lewis lung carcinoma indicated that mitoxantrone and mitoxantrone-loaded casein-polyglutamic acid microspheres exhibited lower toxicity when administered intratumorally.

First pregnancies and livebirths from transfer of sodium alginate encapsulated embryos in a rodent model.

OBJECTIVE: To determine the effect of sodium alginate encapsulation of rodent embryos on in vitro embryonic cleavage rates, implantation rates, and livebirth rates, and to find the in vivo degradation time for the capsules. DESIGN: Studies were conducted using both CB6F1 mice and Golden Syrian hamsters. RESULTS: Capsules made with 3.0% sodium alginate degraded in vivo within 24 to 48 hours after transfer. In vitro embryonic cleavage of encapsulated embryos was not impaired, nor were implantation rates in CB6F1 mice. Finally, 8.6% of transferred encapsulated embryos resulted in livebirths. CONCLUSIONS: Encapsulation of rodent embryos in 3.0% sodium alginate is not detrimental to embryonic development, implantation rates, or fetal development. Because the capsule degrades within 48 hours after transfer, encapsulating embryos may be beneficial for human in vitro fertilization and embryo transfer.

A prospective three-year study of response properties of normal subjects and patients during automated perimetry.

PURPOSE: The purpose of this study is to evaluate prospectively the reliability characteristics of patients undergoing automated perimetry over a 3-year period and compare these results with the results of previous investigations. METHODS: The subjects included 48 normal observers, 32 ocular hypertensive subjects, and 19 patients with early glaucomatous visual field loss. Both eyes were tested annually for 3 years with automated perimetry, using the standard procedures for the Humphrey Field Analyzer. Fixation losses, false-positive errors, false-negative errors, and short-term variability (double determinations) were evaluated. RESULTS: Short-term variability was slightly higher for the early glaucoma group than for the normal observer and ocular hypertensive groups, but there were no meaningful changes in short-term variability over 3 years. False-positive errors were very low in all three groups throughout the investigation. False-negative errors were slightly higher in the early glaucoma group, but all three groups had relatively low false-negative error rates throughout the study. Fixation losses were the most common source of unreliable results. The number of fixation losses decreased for the second and third years of the study. CONCLUSION: Contrary to a previous report, a relatively low number of unreliable tests were found for both initial and follow-up visits. The majority of unreliable visual field tests were sporadic events. Only a few subjects repeatedly produced unreliable test results. The authors conclude that automated perimetry can provide a reliable means of following patients over extended periods of time.

Response properties of normal observers and patients during automated perimetry.

Automated perimetry was performed on both eyes of 54 normal subjects, 36 patients with ocular hypertension and normal visual fields, and 20 patients with early glaucomatous visual field loss to evaluate false-positive errors, false-negative errors, fixation losses, consistency of double determinations, and testing time. For all subject groups and response measures, large interindividual variation was found. No meaningful age-related changes were obtained for false-negative errors, false-positive errors, fixation losses, or consistency of double determinations. Contrary to earlier reports, we found a low number of normal subjects and patients exceeding the 33% false-positive and false-negative limits established for the Humphrey Field Analyzer. A large number of normal subjects and patients, however, exceeded the 20% limits for fixation losses.

Age-related changes in the central visual field for short-wavelength-sensitive pathways.

The sensitivity of short-wavelength-sensitive (SWS) cone pathways throughout the central 30-deg visual field was determined in both eyes of 62 normal volunteers between the ages of 20 and 72 years. We found an average SWS cone pathway sensitivity decrease with age of approximately 0.15 log unit per decade. The sensitivity reduction was approximately linear, with a slightly larger decrease beyond the age of 50 years. The age-related SWS cone pathway sensitivity reductions also became larger as a function of increasing stimulus eccentricity. Measurements of ocular-media absorption characteristics in each eye revealed that 30-40% of the age-related sensitivity loss could be attributed to reductions in transmission of short-wavelength light by the ocular media. After corrections for preretinal media transmission loss, the decrease in the sensitivity of SWS cone pathways with age was approximately 0.09 log unit per decade. This age-related loss is greater than age-related sensitivity decreases in the middle-wavelength-sensitive and/or long-wavelength-sensitive cones (approximately 0.06 to 0.07 log unit per decade). In the age group older than 60 years, there was an inverse relationship between media-corrected SWS cone pathway sensitivity and media absorption characteristics (i.e., media-corrected SWS cone pathway sensitivity was higher in eyes with lower media transmission of short wavelengths). This relationship was not so evident for younger subjects. A similar inverse relationship between transmission loss in the ocular media and SWS cone pathway sensitivity was found between left and right eyes of the same individual.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of the polyurethane sponge as a delivery system for aryl 4-guanidinobenzoates.

The Today Contraceptive Sponge was evaluated as a vehicle for the delivery of aryl 4-guanidinobenzoates (AGs) which are highly active sperm acrosin inhibitors. Studies in animals have shown that several AGs are more potent vaginal contraceptives and less irritating to the vagina than nonoxynol-9 (N-9), the most frequently used active ingredient in commercial vaginal contraceptive formulations. Neither nonoxynol-9 nor the material that could be solubilized from the sponge matrix altered the enzyme-inhibitory activity of 4'-acetamidophenyl 4-guanidinobenzoate HCl (AGB), 4'-carboxyphenyl 4-guanidinobenzoate HCl (EGB) or 4'-carbomethoxyphenyl 4-guanidinobenzoate HCl (MSGB). Besides being acrosin inhibitors, all three AGs exhibited antimotility activity towards human spermatozoa, EGB being as potent as N-9. The antimotility effects of the AGs and N-9 were additive. For subsequent studies, AGB was used as the model compound. Manufacture of the AGB-containing sponges did not affect the chemical structure of AGB. Good release rates of AGB were obtained from the sponges over a 7-day period. The release rates were 20-50% higher when the sponges also contained N-9. These results indicate that certain AGs exert a dual contraceptive action on spermatozoa by inhibiting both the sperm enzyme acrosin and sperm motility. Furthermore, the polyurethane sponge appears to be a convenient and satisfactory long-term delivery system for the AGs. A mixture of N-9 and AG can be used clinically because these compounds have no adverse effects on each other.

Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo.

In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.