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Biomedical subjects

Robert Ritch

Publications and source records attributed to Robert Ritch.

At least 37 records · Page 2Linked to original sources

Central corneal thickness is not related to anterior scleral thickness or axial length.

PURPOSE: To examine the relationship between central corneal thickness (CCT), scleral thickness (ST), refractive error, and axial length. METHODS: One hundred forty eyes of 140 patients with no previous history of intraocular surgery were enrolled. Axial length, CCT, and ST were measured ultrasonically. Radial ultrasound biomicroscopy (UBM) images were obtained by a single examiner scanning the temporal corneoscleral limbus. ST was measured independently on the UBM images by two masked observers at scleral spur (ST1) and 2.0 and 3.0 mm posterior to it (ST2 and ST3). RESULTS: Mean patient age was 57.0+/-15.7 (SD) years, and mean refractive error was -1.3+/-5.0 diopters. Intraclass correlation coefficients >0.75 indicated excellent agreement between the two observers for all ST measurements. There was a positive and significant correlation between CCT and ST1 (r=0.27, P=0.001) but not between CCT and ST2 (r=0.02, P=0.8), ST3 (r=0.06, P=0.5), refractive error (r=0.08, P=0.3), or axial length (r=0.07, P=0.4). CONCLUSIONS: CCT correlates with ST only at the scleral spur and is unrelated to refractive error or axial length. This study does not support the hypothesis that a thin CCT is a surrogate marker for abnormal scleral or laminar thickness as an independent cause of increased glaucoma risk.

Body Weights and Measures↗

Detecting early functional damage in glaucoma suspect and ocular hypertensive patients with the multifocal VEP technique.

PURPOSE: To determine whether the multifocal visual evoked potential (mfVEP) technique can detect early functional damage in ocular hypertensive (OHT) and glaucoma suspect (GS) patients with normal standard achromatic automated perimetry (SAP) results. PATIENTS AND METHODS: Twenty-five GS patients (25 eyes), 25 patients with OHT (25 eyes), and 50 normal controls (50 eyes) were enrolled in this study. All GS, OHT and normal control eyes had normal SAP as defined by a pattern standard deviation and mean deviation within the 95% confidence interval and a glaucoma hemifield test within normal limits on the Humphrey visual field 24-2 program. Eyes with GS had optic disc changes consistent with glaucoma with or without raised intraocular pressure (IOP), and eyes with OHT showed no evidence of glaucomatous optic neuropathy and IOPs >or=22 mm Hg. Monocular mfVEPs were obtained from both eyes of each subject using a pattern-reversal dartboard array with 60 sectors. The entire display had a radius of 22.3 degrees. The mfVEPs, for each eye, were defined as abnormal when either the monocular or interocular probability plot had a cluster of 3 or more contiguous points with P<0.05 and at least 2 of these points with P<0.01. RESULTS: The mfVEP results were abnormal in 4% of the eyes from normal subjects. Abnormal mfVEPs were detected in 20% of the eyes of GS patients and 16% of the eyes of OHT patients. Significantly more mfVEP abnormalities were detected in GS patients than in normal controls. However, there was no significant difference in mfVEP results between OHT patients and normal controls. CONCLUSIONS: The mfVEP technique can detect visual field deficits in a minority of eyes with glaucomatous optic disks and normal SAP results.

Disease Progression↗

Assessment of a race-specific normative HRT-III database to differentiate glaucomatous from normal eyes.

PURPOSE: To determine if a new, normative, race-specific database enhances the ability of confocal scanning laser ophthalmoscopy to differentiate normal from glaucomatous eyes. METHODS: One eye of eligible normal and glaucoma patients was enrolled. All subjects underwent a complete ophthalmologic examination, standard achromatic perimetry (SITA-SAP, 24-2), and confocal scanning laser ophthalmoscopy [Heidelberg retinal tomograph (HRT-II)] within 1 month of enrollment. Racial groups were defined by self-report. Glaucoma was defined by the existence of reproducible SAP loss (pattern standard deviation <5% and/or Glaucoma Hemifield Test outside normal limits) on 2 consecutive fields. Normal subjects had 2 normal visual fields (pattern standard deviation >5% and Glaucoma Hemifield Test within 97% normal limits) and a normal clinical examination. HRT-II examinations were exported to the HRT-III software, which includes a large race-specific normative database consisting of 733 white and 215 black eyes. Moorfields regression analysis (MRA) for the most abnormal optic disc sector was compared between the HRT-II (MRA2) and the HRT-III software before (MRA3-B) and after (MRA3-A) adjustment for race. Sectors outside the 99.9% confidence interval limits ("outside normal limits") were determined to be abnormal. RESULTS: We enrolled 124 black (52 glaucoma, 72 normal) and 96 white (32 glaucoma, 64 normal) subjects. Mean age was 51+/-13 years and 50+/-16 years for blacks and whites, respectively (P = 0.45). Visual field mean deviation was -7.3+/-6.7 db for glaucomatous eyes and -0.4+/-1.1 db for normal eyes (P < 0.001). Sensitivity and specificity for the HRT-II was 71.9% and 95.3%, respectively, for white subjects and 50.0% and 98.6%, respectively, for black subjects. Using the expanded HRT-III database, analysis yielded a sensitivity of 81.3% and specificity of 93.8% for whites and a sensitivity of 71.2% and specificity of 86.1% for blacks. After an adjustment for black ethnicity was made in the HRT-III program, the sensitivity and specificity for blacks was 65.4% and 90.3%, respectively. CONCLUSIONS: A new, larger, race-specific HRT-III database increases sensitivity while maintaining specificity for whites and increases sensitivity but decreases specificity for blacks. New software and databases based on race require careful scrutiny before use in clinical practice.

Adult↗

Early diagnosis of exfoliation syndrome in the offspring of affected patients.

PURPOSE: To determine whether conjunctival biopsy in the offspring of patients with exfoliation syndrome (XFS) can provide early diagnosis of the disease. METHODS: Patients with XFS with or without glaucoma were invited to ask their sons and daughters over the age of 40 years to participate in the study. After a complete eye examination, those without clinically evident XFS underwent conjunctival biopsy. The specimens were examined by transmission electron microscopy. RESULTS: A total of 17 sons and daughters (seven men, 10 women) of 17 patients were enrolled. Their mean age was 50.3 +/- 8 years. Twelve specimens were negative and five presented precursor material evidence of typical exfoliation material. CONCLUSION: Evidence of early deposition of exfoliation material can be found in the conjunctiva of the middle-aged offspring of patients with XFS, substantiating the existence of a hereditary predisposition to this disease.

Adult↗

Control of filtering bleb structure through tissue bioengineering: An animal model.

PURPOSE: To devise a means of providing controlled resistance between the anterior chamber and the subconjunctival space after trabeculectomy by implantation of a biodegradable, porous collagen matrix. METHODS: Matrices were implanted in the right eyes of 17 rabbits after trabeculectomy, while left eyes served as surgical controls. The scleral flap was sutured loosely, and the implant provided pressure on the scleral flap to reduce overfiltration. Trabeculectomy in the control eyes was performed with tight sutures using standard methodology. Intraocular pressure (IOP) was measured before surgery and on days 3, 7, 14, 21, and 28 after surgery. Masson trichrome and alpha-smooth muscle actin stains were used for histologic study of the filtering blebs. RESULTS: The initial postoperative IOP reduction was approximately equal, at 14% to 16%, for both groups. In the implanted group, the IOP continued to decrease to 55% below baseline at day 28 as the implant gradually degraded. In the control group, IOP had returned to the preoperative level by day 21. Histologic examination with Masson trichrome and alpha-smooth muscle actin stains showed a prominent bleb in the implanted group compared with scar formation and limited bleb formation in the control group. CONCLUSIONS: Implantation of a biodegradable, porous collagen matrix in the subconjunctival space offers the potential for a new means of avoiding early scar formation and maintaining long-term IOP control by creating a loosely structured filtering bleb.

Absorbable Implants↗

A comparison between multifocal and conventional VEP latency changes secondary to glaucomatous damage.

PURPOSE: To compare latencies of conventional visual evoked potentials (cVEPs) and multifocal VEPs (mfVEPs) in the same patients. Previous reports of prolonged cVEP latency suggest a vehicle for detecting abnormal ganglion cells and for monitoring neuroprotection. METHODS: Seventy-five glaucomatous eyes (47 patients), 75 eyes with suspected glaucoma (46 patients), and 41 control eyes (22 subjects) underwent achromatic automated perimetry and mfVEP and cVEP testing. The mfVEP stimulus was a scaled dart board with 60 sectors; each sector was a pattern-reversing checkerboard. The cVEP stimulus was a reversing checkerboard with checks of either 15 minutes or 60 minutes in width. RESULTS: Relatively few glaucomatous eyes had latencies that fell outside the range of control eyes, and there was little difference between the cVEP and mfVEP results. In the glaucoma group, 12.3% (15 minutes cVEP), 8% (60 minutes cVEP), and 17.3% (mfVEP) of the eyes and 5.3% (15 minutes cVEP), 6.7% (60 minutes cVEP), and 5.3% (mfVEP) of the suspect eyes exceeded the normal range. The glaucomatous eyes had, on average, relatively small increases in latency, compared with the control or suspect groups. Further, the latency of both the mfVEP and cVEP bore no obvious relationship to the mean deviation of the visual field. CONCLUSIONS: Contrary to previous reports, prolonged VEP delays were present in a minority of patients with glaucoma. Either a delayed VEP is not a good indicator of damaged, as opposed to dead, retinal ganglion cells, or there are relatively few patients who exhibit evidence of damaged ganglion cells.

Adolescent↗

Latanoprost therapy reduces the levels of TGF beta 1 and gelatinases in the aqueous humour of patients with exfoliative glaucoma.

The aim of the present study was to evaluate the effect of latanoprost monotherapy on the aqueous humour concentrations of TGF-beta1, MMP-2, TIMP-2, MMP-9 and gelatinolytic activity in patients treated for exfoliative glaucoma (XFG). Aqueous samples from 50 XFG patients treated with latanoprost and 50 age-matched XFG patients treated with timolol were collected during phacoemulsification cataract surgery. The concentrations of TGF-beta1, MMP-2, TIMP-2, MMP-9 and gelatinase activity were determined by commercial immunoassays. The mean active TGF-beta1 concentration in the aqueous was significantly lower in XFG patients treated with latanoprost compared with those treated with timolol (3.1 +/- 0.65 vs 13.4 +/- 1.5 pg ml(-1)); (P = 0.0014). The mean total MMP-2 concentration was lower in latanoprost treated patients (31.75 +/- 3.8 vs 81.5 +/- 7.2 ng ml(-1)); (P < 0.0001). The TIMP-2 concentration was also lower in XFG-latanoprost treated patients (73.8 +/- 6.81 vs 101.28 +/- 7.29 ng ml(-1)); (P = 0.0096). Latanoprost monotherapy has a marked effect on the aqueous concentration of TGF-beta1, MMP-2 and TIMP-2 in XFG patients. A better understanding of its effect on the pathobiology of the disease may lead to its earlier use in the disease process to prevent progression from XFS to XFG.

Adrenergic beta-Antagonists↗

Dynamic changes in reactive oxygen species and antioxidant levels in retinas in experimental glaucoma.

We investigated the balance of free radicals in retinas at various time points after chronically elevating intraocular pressures in rats. The left eyes of female Wistar rats were divided into five intraocular pressure elevation (IOPE) subgroups after cauterization of three episcleral veins (1 day, 3 days, 1 week, 3 weeks, and 5 weeks) and time-related sham controls. Chemiluminescence levels were examined in isolated retinas. The nitroblue tetrazolium (NBT) incubation method was also performed to confirm the superoxide expression. The activities of antioxidant enzymes and lipid peroxides in isolated retinas were detected by spectrophotometry. In the IOPE group, the intraocular pressure after cauterization was around 22-30 mm Hg; chemiluminescence levels of isolated retinas were significantly elevated on day 3 and week 1; there were more NBT-positive retinal ganglion cells on day 1 and day 3; lipid peroxidation also increased significantly from day 1 and came back to the baseline on week 5; the activities of superoxide dismutases and catalase rose on week 1. Intraocular pressure elevation was shown to change the free radical balance. We suggest that free radicals and their oxidative stresses may play a role in the early stage of glaucoma in causing retinal ganglion cell death in our rat model.

Animals↗

Identification of a novel adult-onset primary open-angle glaucoma (POAG) gene on 5q22.1.

Glaucoma is a leading cause of blindness in virtually every country. Development of an accurate diagnostic test for presymptomatic detection of individuals at risk is an urgent requisition for this condition. Herein, we report mapping of a new adult-onset primary open-angle glaucoma (POAG) locus on 5q22.1 (GLC1G) and identification of its defective gene. Mutation screening of seven candidate genes from the GLC1G critical region (approximately 2 Mb between D5S1466 and D5S2051) identified only one significant alteration in the WDR36 (WD40-repeat 36) gene. This mutation (i.e. D658G) was segregated in all affected members of our first GLC1G-linked family but it was absent in 476 normal control chromosomes. Further screening of WDR36 in a total of 130 POAG families revealed 24 DNA variations. Overall, four mutations (N355S, A449T, R529Q and D658G) were identified in 17 (5.02-6.92%) unrelated POAG subjects, 11 with high-pressure and six with low-pressure glaucoma. These mutations were absent in a minimum of 200 normal control chromosomes and, further they were conserved between WDR36 orthologues in mouse, rat, dog, chimp and human. WDR36 is a novel gene with 23 exons, which encodes for 951 amino acids and a protein with multiple G-beta WD40 repeats. By northern blotting, two distinct mRNA transcripts of 5.9 and 2.5 kb were observed in human heart, placenta, liver, skeletal muscle, kidney and pancreas. WDR36 gene expression in lens, iris, sclera, ciliary muscles, ciliary body, trabecular meshwork, retina and optic nerve were established by RT-PCR. In mouse, two transcripts of 3.5 and 2.9 kb showed analogous expression patterns to human. mRNA expressions were detected in 7-, 11-, 15- and 17-day-old developing mouse embryos. In summary, WDR36 is a novel causative gene for adult-onset POAG at the GLC1G locus. Specific ocular expressions and observed mutations are consistent with WDR36 role in etiology of both high- and low-pressure glaucoma.

Amino Acid Substitution↗

Ciliary body thickness increases with increasing axial myopia.

PURPOSE: To assess the relationship between ciliary body thickness and refractive error. DESIGN: Prospective observational case series. METHODS: We enrolled 75 eyes of 75 patients with no history of intraocular surgery or use of anti-glaucoma medication. Axial length was measured by A-scan ultrasonography. Ciliary body thickness (CBT) was measured by two masked observers on radial-section images of the temporal corneoscleral limbus, acquired with ultrasound biomicroscopy (UBM) at 2 and 3 mm posterior to the scleral spur (CBT2 and CBT3, respectively). RESULTS: Refractive error was inversely correlated with CBT2 and CBT3 (r = -.64 and r = -.52, P < .0001, respectively). Axial length was correlated with CBT (r = .66 and r = .57, P < .0001, for CBT2 and CBT3, respectively). CONCLUSION: CBT increases with increasing myopia and axial length.

Body Weights and Measures↗

Assessment of central corneal thickness using optical coherence tomography.

PURPOSE: To demonstrate the capability of model OCT3 optical coherence tomographer to evaluate central corneal thickness (CCT) in normal human corneas in vivo and compare the results with the those of standard ultrasound (US) pachymetry and Orbscan. SETTING: New York Eye & Ear Infirmary Resident Clinic, New York, New York, USA. METHODS: The CCT in 22 eyes of 11 subjects was determined with the OCT3 (Carl Zeiss Meditec), Orbscan (Bausch & Lomb, Inc.), and US pachymetry (DGH Technology, Inc.). Three central corneal scans of each eye were obtained using the OCT3. First, OCT3 data were processed using the standard OCT software program (OCT3(std)). Second, OCT3 raw data were exported and measurements were repeated using Scion Image for Windows program (OCT3(sci)). The OCT3 and Orbscan results were compared with the mean of 5 US pachymetry measurements in each eye. RESULTS: The OCT3(std), OCT3(sci), and Orbscan CCT measurements showed high correlations with US pachymetry (r=0.981, r=0.984, and r=0.942, respectively; P<.0001). Bland-Altman analysis showed a high level of agreement between US pachymetry and OCT3 techniques but not Orbscan. High repeatability for OCT3(std) (r(2)=0.05) and OCT3(sci) (r(2)=0.01) was also seen. CONCLUSION: Results show the OCT3 is an accurate, noninvasive, and reproducible technique for evaluation of CCT.

Adult↗

Complementary therapy for the treatment of glaucoma: a perspective.

Although neuroprotective strategies and pharmaceutical agents have been initiated in the treatment of numerous disorders of the central and peripheral nervous systems, including trauma, epilepsy, stroke, Huntington disease, amyotrophic lateral sclerosis,and AIDS dementia, none have yet been applied to the treatment of glaucoma. A prospective, placebo-controlled, multi-institutional trial of memantine is underway. One would not expect the treatment modalities that form the bases of nonpharmaceutical, traditional medical systems to be used to lower IOP. Glaucoma was unknown when these medicinal treatments were developed over the centuries. Their primary use is in improving the cardiovascular and immune systems and in what is now called neuro-protection. Rather than single compounds that target a specific receptor and have demarcated side effects in other systems, plant products are a blend of many compounds and, according to those most versed in them, they achieve a balanced therapy, helping in specific symptomatic complexes while reducing side effects through ameliorating effects in other areas. It is not insignificant that, now that the rain forests are rapidly dwindling, together with their inhabitants and the knowledge of medicinal plants (especially in South America), the pharmaceutical companies are spending large amounts of money in a sudden, almost frantic attempt to gather the knowledge about rainforest plants before all has been completely lost. Proof of effects clinically in a chronic disease such as glaucoma remains largely lacking, and controlled trials are unlikely to be initiated, except perhaps through the National Institutes of Health, because these compounds have been in the public domain for many years. Perhaps those as yet unknown or un-recorded are patentable and perhaps these include drugs known only to small surviving communities of hunter-gatherers, which explains the pharmaceutical interest in these areas. When more accurate and rapid means of assessment of progression of glaucomatous damage than perimetry and optic nerve head photography are eventually developed and trials can be reduced in time, number of subjects, or even the use of nonhuman subjects for the bulk of studies, studies could be done for verification of effect of various compounds and also comparative studies. At the present time, GBE is the best documented of all the complementary medicinal agents and seems to have the greatest potential value. Ginkgo biloba extract has numerous properties that theoretically should be beneficial in treating non-IOP-dependent mechanisms in glaucoma. Its multi-ple beneficial actions, including increased ocular blood flow, antioxidant activity, platelet activating factor inhibitory activity, nitric oxide inhibition, and neuroprotective activity, combine to suggest that GBE could prove to be of major therapeutic value in the treatment of glaucoma.

Complementary Therapies↗

The Low-pressure Glaucoma Treatment Study (LoGTS) study design and baseline characteristics of enrolled patients.

OBJECTIVE: The Low-Pressure Glaucoma Treatment Study (LoGTS) seeks to evaluate visual field stability in low-pressure glaucoma patients randomized to intraocular pressure reduction in both eyes with topical twice daily brimonidine tartrate 0.2% versus twice daily timolol maleate 0.5%. This article describes the LoGTS design and presents baseline characteristics of the subjects. DESIGN: Randomized, multicenter, double-masked clinical trial. PARTICIPANTS: Low-pressure glaucoma patients 30 years of age or older were identified. Exclusion criteria included an untreated pressure of more than 21 mmHg, advanced visual field loss, and contraindications to study medications. INTERVENTIONS: Randomization of both eyes to double-masked monotherapy with brimonidine or timolol. Follow-up visits included Humphrey 24-2 full-threshold perimetry, tonometry every 4 months, and annual optic disc photography. MAIN OUTCOME MEASURE: Progression of visual field loss. RESULTS: One hundred ninety patients were randomized between 1998 and 2000. Mean age (+/-standard deviation) was 64.9+/-10.7 years. Women comprised 59.5% of the patients. Fifty-three patients (27.9%) had unilateral field loss. The 137 patients with bilateral field loss were older than those with unilateral field loss: 65.7 versus 62.3 years of age (P<0.05). Mean untreated diurnal intraocular pressures were similar between the eyes of the bilateral patients (mean, 15.5 mmHg in both eyes) and unilateral patients (mean, 16.0 mmHg in field loss vs. 15.6 mmHg in fellow eyes). Visual field mean deviation for all eyes was -5.4+/-4.7 decibels. Central corneal thickness in 168 phakic patients was 543 +/- 35 microm (range, 435-655 microm); thickness was less than 500 microm in 15 eyes and was more than 600 microm in 11 eyes. Mean vertical cup-to-disc ratio for all eyes was 0.67+/-0.15. Unilateral field loss patients had a larger cup-to-disc ratio in the field loss eye (0.75+/-0.12) than the fellow eye with a normal field (0.60+/-0.17, P<0.0001). Disc hemorrhage was present at baseline in 29 patients (32 eyes). CONCLUSIONS: The LoGTS was successfully able to recruit and enroll patients with open-angle glaucoma and statistically normal intraocular pressure into a longitudinal, prospective clinical trial comparing 2 different glaucoma medications. Baseline characteristics of note were a preponderance of females, unilateral field loss in 27.9% of participants, and frequent optic disc hemorrhage. Central corneal thickness had a normal distribution and did not account for false low-pressure measurements in LoGTS patients.

Adult↗

The influence of peripheral iridotomy on the intraocular pressure course in patients with pigmentary glaucoma.

PURPOSE: To evaluate the influence of laser peripheral iridotomy on the long-term intraocular pressure course for patients with pigmentary glaucoma. PATIENTS AND METHODS: Retrospective analysis of data contributed by members of the American Glaucoma Society on patients with bilateral pigmentary glaucoma, who received uniocular laser iridotomy. The main outcome measure was the post-laser intraocular pressure course of the treated eyes, compared with the fellow, untreated eyes. RESULTS: Sixty patients were included in the study, 46 of whom were observed for a minimum of 2 years (mean 70.3 +/- 26.0 months; range 24-113 months). Among the 14 patients who were observed for less than 2 years, the mean intraocular pressure in the treated eyes increased 0.36 +/- 2.63 mm Hg, compared with the fellow, untreated eyes. Among the 46 patients, observed for 2 years or more, the mean intraocular pressure in the treated eyes decreased 4.0 +/- 5.4 mm Hg, compared with 1.9 +/- 3.8 mm Hg in the fellow eyes (P = 0.005). However, analysis by linear models indicates that a higher mean baseline intraocular pressure in the treated eyes accounts for the apparent treatment effect of laser peripheral iridotomy. CONCLUSION: The study does not provide support for the benefit of laser peripheral iridotomy in the long-term intraocular pressure control of patients with pigmentary glaucoma, when the data are subjected to rigid statistical analysis. This does not disprove the benefit of laser iridotomy in this patient population, but underscores the need for a large, prospective study to address the question.

Adult↗

Central corneal thickness measurement in clinical practice.

OBJECTIVE: To determine if a single measurement of central corneal thickness (CCT) is an adequate sample to aid in glaucoma risk assessment in clinical practice. METHODS: Central corneal thickness was measured by ultrasound pachymetry (mean of 15 measurements for each eye) on two separate occasions at least one month apart (range, 33 to 610 days). Eyes with a history of prior incisional surgery or corneal pathology were excluded. RESULTS: Ninety-eight eyes of 98 patients (43 male, 55 female) were enrolled. Mean age was 61.2 +/- 15.5 years. Mean inter-test period was 276 +/- 124 days. No significant difference in mean CCT was observed between the two visits (549 +/- 41 microm versus 548 +/- 42 microm, P = 0.4, two-tailed, paired t test). Measured CCT values differed by more than 20 microm in 20 eyes (20.4%), whereas CCT difference of at least 40 microm was seen in 5 eyes (5.1%). There was no correlation between the measured or absolute difference in CCT and IOP (r = -0.016, P > 0.43), inter-test time period (r = 0.072, P > 0.23), and glaucoma diagnosis. CONCLUSION: Central corneal thickness measurements in this study differed by at least 20 microm in 20% of eyes. This has important implications for risk assessment, management, and follow-up of patients with glaucoma and related disorders. Factors affecting CCT measurement, such as examiner error or true alterations in corneal thickness, require continued investigation.

Adolescent↗

Hypophosphorylation of aqueous humor sCD44 and primary open-angle glaucoma.

PURPOSE: The ectodomain of CD44, the principal receptor for hyaluronic acid (HA), is shed as a 32-kDa fragment-soluble CD44 (sCD44)-which is cytotoxic to trabecular meshwork (TM) cells and retinal ganglion cells (RGCs) in culture. The purpose of this study was to characterize sCD44 further by determining the phosphorylation of aqueous humor sCD44 in normal and primary open-angle glaucoma (POAG). METHODS: Aqueous humor samples of patients were subjected to CD44 enzyme-linked immunosorbent assay (ELISA) and two-dimensional (2-D) polyacrylamide gel electrophoresis, followed by Western blot analysis with anti-CD44, anti-serine/threonine, and anti-tyrosine phosphospecific antibodies, to determine sCD44 concentration, isoelectric point (pI), and phosphorylation, respectively. The bioactivity of hypophosphorylated sCD44 was tested in cell culture and HA affinity columns. RESULTS: Two-dimensional Western blot analysis revealed that the representative pI of the 32-kDa sCD44 was 6.96 +/- 0.07 in POAG versus 6.38 +/- 0.08 in normal (P < 0.0004). Enzymatic dephosphorylation of sCD44 resulted in a basic shift in the pI. The normal aqueous humor sCD44 was positive for serine-threonine phosphorylation; however, POAG sCD44 was hypophosphorylated. Hypophosphorylated sCD44 was more toxic to TM and RGC cells than standard sCD44, and hypophosphorylated sCD44 had decreased affinity to HA, particularly with increased pressure. CONCLUSIONS: POAG aqueous is characterized by posttranslational change in the pI of sCD44 and hypophosphorylation, which clearly distinguished POAG from normal aqueous humor. The high toxicity and low HA-binding affinity of hypophosphorylated sCD44 may represent specific pathophysiologic features of the POAG disease process.

Aqueous Humor↗

The pattern electroretinogram in glaucoma patients with confirmed visual field deficits.

PURPOSE: To better understand the relationship between the amplitude of the pattern electroretinogram (PERG) and visual loss, measured with static automated perimetry. METHODS: Transient PERGs were recorded in 15 patients (31-77 years) and 16 normal individuals (26-65 years). An eye was considered to have glaucomatous damage only if there was an abnormal disc, an abnormal 24-2 Humphrey visual field result (pattern stand deviation, glaucoma hemifield test, and cluster) and an abnormal multifocal visual evoked potential. All the worse (more affected) eyes of the patients and six of the better eyes met these criteria. The N95 amplitude of the PERG was measured from the positive peak (P50) at approximately 50 ms to the trough at approximately 95 ms. The ratio of N95 to P50-the N95 amplitude divided by the P50 amplitude-was also measured. RESULTS: First, the PERG was within normal limits for 4 (26.7%) of the worse eyes. Overall, 6 (28.6%) of the 21 eyes that met the criteria for glaucomatous damage had normal PERGs on both PERG measures. Because the normal individuals were younger than the patients, an even larger number of normal PERGs might be expected with an age-appropriate control group. Second, the N95 amplitude was nonlinearly related to visual field sensitivity when sensitivity was plotted on a linear plot. Small field losses were associated with disproportionately large losses in PERG amplitude. Third, the PERG from both eyes of a patient were very similar, even when the visual fields suggested very different levels of damage. CONCLUSIONS: These results are consistent with the view that very early damage can affect the PERG, even before the visual field shows a loss. At the same time, it is clear that patients with clear glaucomatous damage can have normal-appearing PERGs. An explanation is proposed to account for these findings.

Adult↗