A Plasmodium chabaudi protein contains a repetitive region with a predicted spectrin-like structure.

cDNA and genomic DNA clones covering the entire open reading frame (ORF) for a Plasmodium chabaudi 96V protein were isolated. From the first ATG codon the intronless gene codes for a 229-kDa protein. Antisera raised against recombinant polypeptides coded by two different regions of the gene reacted with a 240/225-kDa doublet on Western blots of parasite extracts. In immunofluorescence studies the same sera detected the antigen at the apical end of the merozoite, possibly in rhoptry organelles. In Western blotting experiments the recombinant polypeptides were recognised by antibodies induced by natural infection. A 364-amino acid residue repetitive region, based on 32 11-mer repeats divided by two 6-mer repeats into three blocks, is located in the centre of the protein. Analysis of this repetitive region led us to propose a model in which each of the three units forms an alpha-helical coiled-coil triple-helix containing a possible leucine-histidine zipper. Each unit resembles in structure the units present in spectrin. The repeat region is flanked by predicted heptad based alpha-helical coiled-coil regions, and we propose that the protein forms a dimer. The 229-kDa protein has the overall character of a cytoskeletal protein. We have named the 229-kDa protein repetitive organellar protein (ROPE) and suggest that ROPE may be involved in the process of invasion, possibly by interacting with the erythrocyte cytoskeleton, and that the leucine histidine-zipper may be involved in molecular mimicry of spectrin.

Current status of the Plasmodium falciparum genome project.

The Plasmodium falciparum Genome Project is a collaborative effort by many laboratories that will provide detailed molecular information about the parasite, which may be used for developing practical control measures. Initial goals are to prepare an electronically indexed clone bank containing partially sequenced clones representing up to 80% of the parasite's genes and to prepare an ordered set of overlapping clones spanning each of the parasite's 14 chromosomes. Currently, clones of genomic DNA, prepared as yeast artificial chromosomes, are arranged into contigs covering approximately 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than contigs covering approximately 70% of the genome of parasite clone 3D7, gene sequence tags are available from more than 20% of the parasite's genes, and approximately 5% of the parasite's genes are tentatively identified from similarity searches of entries in the international sequence databases. A total of > 0.5 Mb of P. falciparum sequence tag data is available. The gene sequence tags are presently being used to complete YAC contig assembly and localize the cloned genes to positions on the physical map in preparation for sequencing the genome. Routes of access to project information and services are described.

Variability of automated visual fields in clinically stable glaucoma patients.

The total variability of the visual field was measured in 20 patients with open-angle glaucoma who appeared to be clinically stable and well controlled on medical therapy. All patients had at least four visual fields performed on the Octopus 201 perimeter with at least 12 months follow-up since their first visual field. The four most recently performed visual fields were analyzed. Two different methods for calculating total variability were used. One was based on the variance of the threshold determinations and the other was based on the range. The average total variability per subject was 2.8 decibels (db) using the variance-based calculation and 5.1 db using the range-based calculation. Ninety-five percent of the test locations had a variability of less than 6 db by the variance-based calculation method and 13 db by the range-based calculation method. We discuss the possibility of using this type of data to develop criteria for detection of progressive visual field loss in glaucoma.

Early visual field disturbances in glaucoma.

Twenty-two eyes of 22 patients with initially normaly visual fields developed glaucomatous field defects. In 13 of these, the development of the definitive field defect was preceded by a localized minor disturbance in the area where the defect appeared subsequently. In a control group of 22 ocular hypertensives without field defects, six eyes had localized disturbances similar to those that preceded the field defects in the study group. This type of minor localized disturbance may represent an early glaucomatous visual change detectable before the appearance of definitive scotomas.

Trabeculectomy and the progression of glaucomatous visual field loss.

Twenty-four eyes of 20 patients with chronic open angle glaucoma who had a trabeculectomy were studied retrospectively. Trabeculectomy resulted in a significant lowering of mean intraocular pressures and improvement of pressure control for the group. Progression of visual field defects occurred in all 24 eyes preoperatively, while postoperatively, the fields of 14 eyes showed no change, but the other ten showed further progression. A comparison of the pressures of the eyes showing continued progression after surgery with the eyes showing no further progression revealed no significant difference in the mean preoperative or postoperative pressure or the mean pressure reduction after surgery. Measurements of the quality of the control, however, showed that the quality of pressure control was significantly better in the eyes that did not show progression of field loss postoperatively. Careful postoperative follow-up observation of the visual field remains necessary even after successful surgical pressure reduction.

Variability of static visual threshold responses in patients with elevated IOPs.

We determined the static visual thresholds within 15 degrees of fixation of 36 patients with elevated intraocular pressures but normal visual fields and compared the result with 36 controls matched for age and sex. We found no difference in the mean threshold level between the two groups. We did find a tendency for the patients with elevated IOPs to have greater variability or scatter of their threshold responses close to fixation. We also found the patients had larger cup to disc ratios than the controls.

Optic disc topography in patients with low-tension and primary open angle glaucoma.

Computerized optic disc topographic measurements (cup-disc ratio, neuroretinal rim area, disc volume) and automated visual field parameters (total field loss, mean sensitivity) were similar in 48 eyes with primary open angle glaucoma and 27 eyes with low-tension glaucoma. In open angle glaucoma, the neuroretinal rim area was negatively correlated with the cup-disc ratio and the disc volume. Total field loss was positively correlated with the cup-disc ratio and the disc volume and negatively correlated with the neuroretinal rim area. Eyes with low-tension glaucoma showed a negative correlation between neuroretinal rim area and cup-disc ratio, and between total field loss and rim area. However, low-tension glaucomatous eyes did not have significant correlations between disc volume and rim area and between total field loss and cup-disc ratio or disc volume. Cupping in low-tension glaucoma was broadly sloping, resulting in less disc volume alteration.

A comparison of experienced clinical observers and statistical tests in detection of progressive visual field loss in glaucoma using automated perimetry.

The visual fields of 30 patients (subjects) with glaucoma were sent to six experienced clinicians (observers). Each subject had at least four visual field examinations on the OCTOPUS 201 automated perimeter spanning at least one year. Each observer was asked to review the visual field data of each subject and determine whether the visual fields were stable, improved, or worse over time. The visual field data were then analyzed using six different statistical models. In only 15 of the 30 subjects did at least five of the six human observers agree on the behavior of the visual field. Agreement among the statistical models was better, with at least five of the six models agreeing on 22 of the 30 subjects. It was concluded that there is, at present, no validated technique for detecting progressive visual field loss in glaucoma using automated perimetry when relatively few visual fields are available for analysis.

Bilateral argon laser trabeculoplasty in primary open-angle glaucoma.

We performed bilateral argon laser trabeculoplasty on 34 patients with medically uncontrolled open-angle glaucoma. Preoperative intraocular pressure was greater than 21 mm Hg, with a less than 3-mm Hg difference between the two eyes. Laser treatment (360 degrees) was performed on both eyes within a three-month interval. Mean (+/- S. D.) baseline intraocular pressure was similar in the first- (26.9 +/- 3.7 mm Hg) and second- (26.5 +/- 3.3 mm Hg) treated eyes. One hour after treatment, four first- and four second-treated eyes had a greater than 30% increase in intraocular pressure. The one-hour change in pressure was highly correlated between the two eyes (r = .794, P less than .0001). Intraocular pressure was reduced (P less than .0001) one, two, and three years after treatment in both the first and second-treated eyes. The percentages of first- and second-treated eyes with a pressure of less than or equal to 21 mm Hg were similar at one, two, and three years. Pressure response between the two eyes was correlated (P less than .0001) at year 1 (r = .815), 2 (r = .757), and 3 (r = .886) after laser therapy.

Technique for determining glaucomatous visual field progression by using animation graphics.

The first two visual field examinations of each of 16 glaucoma suspects and 16 glaucoma patients, who were followed up for a median of 7.46 years with seven examinations, were averaged. Three-dimensional color-coded images of the visual field were then generated. After correcting for test-retest variability, the images, as well as additional interpolated images, were aligned and presented in rapid succession to create an animation sequence. Five glaucoma specialists trained themselves to classify the visual fields as either progressing or not progressing. The interobserver and intraobserver agreement rates were then calculated. Perfect agreement (100% concordance) between the observers was obtained for 18 (56.3%) subjects, and at least 80% concordance was obtained for 27 (84.4%) subjects. Of the eight sequences that were repeated to test intraobserver agreement, four of the five observers had a value of at least 87.5%.

Variability and reproducibility of optic disk topographic measurements with the Rodenstock Optic Nerve Head Analyzer.

Variability of optic disk topographic measurements obtained with the Rodenstock Optic Nerve Head Analyzer was determined by obtaining three separate images on one eye of ten normal subjects and nine subjects without glaucoma. Marking of the disk margin was performed in a random and masked fashion on each image three times by three independent observers. The overall variabilities of the measurements of the subjects with glaucoma were not statistically different from those of the normal subjects. Overall variability was about 0.2 mm2 for total disk area, 0.08 for cup/disk ratio, 0.2 mm2 for disk rim area, and 0.07 mm3 for cup volume. The largest component of the variability was the result of acquisition of separate images of the optic disk at different times. Observer inconsistency in marking the disk edge was relatively small. Based on the expected amount of random variability of the measurements, we proposed criteria for detecting significant change in the optic disk over time.

Relationship between baring of circumlinear vessels of the optic disc and glaucomatous visual field loss.

Stereo disc photographs of the eyes of 232 patients with normal or elevated intraocular pressure were reviewed to assess the value of baring of circumlinear vessels of the optic nerve head as a sign of glaucomatous damage. Baring and the presence of glaucomatous visual field defects were significantly correlated, as were this sign and consistent elevation of the intraocular pressure in patients without a visual field defect. Baring was absent in 35% of the eyes with circumlinear vessels and known glaucomatous visual field defects. However, it was present in only 6% of the eyes with normal pressure, a normal visual field and circumlinear vessels. Therefore, this sign should lead to further evaluation.

Progression of glaucomatous field defects despite successful filtration.

It is generally assumed that successful filtering surgery, by maintaining intraocular pressure at a low level, will protect a glaucoma patient's remaining visual field. We present three patients with chronic open angle glaucoma and typical visual field changes. In each case, filtering surgery was performed because of progressive loss of visual filed and inadequate pressure control. Despite excellent pressure levels after operation, field loss continued in the operated eye. Certain genetic and systemic factors may contribute to further loss of visual field in the presence of normal intraocular pressures. We stress the importance of careful and continuous examination of the visual fields in all glaucoma patients regardless of the response of pressure to treatment.

Increased scatter of responses as a precursor of visual field changes in glaucoma.

A patient with ocular hypertension developed a glaucomatous field defect in the right eye 10 years after the initial examination. For several years preceding the appearance of the defect there had been scatter of threshold responses localized to the area where the defect was later found. We suggest that localized scatter may be an early sign of glaucomatous damage to visual function.

Temporal visual field defects in glaucoma.

In a study of 151 glaucomatous eyes with typical nerve fibre bundle defects we found that 4 (3%) had isolated temporal visual field defects. We stress the importance of studying the temporal field in patients with glaucoma.

Location of early glaucomatous visual field defects.

A study of 50 eyes with chronic open-angle glaucoma and early visual field defects showed superior defects to be twice as common as inferior defects. The superior defects tended to be closer to fixation than the inferior defects.

Risk factors for progression of visual field defects in medically treated patients with glaucoma.

A multivariate discriminant analysis of potential risk factors for the progression of visual field defects was performed in 70 patients with chronic open-angle or low-tension glaucoma. Male sex, low diastolic blood pressure and diabetes mellitus were found to be significant risk factors. When the patients with low-tension glaucoma were excluded, a high mean intraocular pressure was identified as a risk factor. It was concluded that there is no reliable way to predict future visual field loss in patients with glaucoma.

Effect of a topical carbonic anhydrase inhibitor, 6-hydroxybenzo[b]thiophene-2-sulfonamide, on intraocular pressure in normotensive subjects.

A prospective randomized clinical trial was carried out to determine the efficacy of 6-hydroxybenzo[b]thiophene-2-sulfonamide, a potent new carbonic anhydrase inhibitor, in lowering intraocular pressure (IOP) in normotensive volunteers. The drug was administered as a 2% suspension twice daily for 1 week to one eye in 10 subjects. Ten other subjects, serving as controls, received a placebo drop to one eye on the same schedule. Subjects and examiners were unaware of whether the drug or placebo was being used. IOP was measured before the study began and twice daily on days 1, 2, 4 and 8 of the study. The drug had no significant effect on IOP. The most likely explanation is failure of an adequate concentration of the drug to reach the ciliary body.