Glaucoma Specialist Detection of Optical Coherence Tomography Suspicious Rim Tissue in Glaucoma and Glaucoma Suspect Eyes.

PURPOSE: To assess glaucoma specialists' detection of optic nerve head (ONH) rim tissue that is thin by optical coherence tomography (OCT) criteria. DESIGN: Reliability analysis. METHODS: Five clinicians marked the disc margin (DM) and rim margin (RM) on stereophotographs of 151 glaucoma or glaucoma suspect eyes obtained within 3 months of OCT imaging. The photo and OCT infrared image for each eye were co-localized and regionalized into 12 sectors relative to the axis between the Bruch membrane opening (BMO) centroid and the fovea. For each clinician, the distance from BMO centroid to their DM (DM radius) and RM (RM radius) was used to generate sectoral rim width (RW) (DM radius-RM radius) and cup-to-disc ratio (CDR) (RM radius/DM radius) estimates. OCT minimum rim width (MRW) was determined by sector. Among all eyes, for each OCT MRW suspicious sector (<5% of OCT normative database), we determined each clinician's detection (clinician CDR ≥ 0.7). RESULTS: Clinicians most commonly failed to detect OCT suspicious rim tissue in the nasal sectors. Among 502 sectors with suspicious OCT MRW, all 5 clinicians rated CDR ≥ 0.7 in only 29.5% and all 5 clinicians rated CDR < 0.7 in 21%. OCT suspicious rim thickness was most common (32% of eyes) in the nasal and inferior sectors. MRW vs clinician RW discordance was greatest nasally, while BMO vs clinician DM discordance was greatest temporally. CONCLUSIONS: Clinicians most commonly failed to detect OCT suspicious rim thickness nasally where suspicious rim tissues were also most common.

Changes in Iridocorneal Angle and Anterior Chamber Structure in Eyes With Anatomically Narrow Angles: Laser Iridotomy Versus Pilocarpine.

PURPOSE: To compare the effects of laser iridotomy (LI) and pilocarpine on iridocorneal angle and anterior chamber structure in anatomically narrow angles (ANAs). MATERIALS AND METHODS: Temporal LI was performed 90 minutes after 2% pilocarpine administration in patients with occludable ANA. Swept-source optical coherence tomography B-scans of the anterior segment were obtained at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. Angle-opening distance (AOD), trabecular-iris surface area (TISA), and angle recess area (ARA) were measured at the temporal, superior, nasal, and inferior quadrants. Anterior chamber depth (ACD) and lens vault (LV) were also measured. AOD, TISA, ARA, ACD, and LV were compared among 3 time points: at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. RESULTS: Twenty-four eyes (24 patients; mean age, 55 y) were included. In all 4 quadrants and globally, AOD, TISA, and ARA increased from baseline after pilocarpine and after LI (all P<0.010). The increase in AOD, TISA, and ARA was greater after LI than after pilocarpine globally and in the temporal and superior quadrants (all P<0.040). ACD decreased and LV increased from baseline after pilocarpine (both P<0.001). Postpilocarpine anterior chambers were shallower with higher LV than post-LI (both P<0.016). CONCLUSION: LI is more effective than pilocarpine in widening the iridocorneal angle without significant shallowing the anterior chamber in eyes with ANA.

Glaucoma Specialist Optic Disc Margin, Rim Margin, and Rim Width Discordance in Glaucoma and Glaucoma Suspect Eyes.

PURPOSE: To quantify the variability of 5 glaucoma specialists' optic disc margin (DM), rim margin (RM), and rim width (RW) estimates. DESIGN: Inter-observer reliability analysis. METHODS: Clinicians viewed stereo-photographs from 214 subjects with glaucoma or ocular hypertension and digitally marked the DM and RM. For each photograph, the centroid of each clinician's DM was calculated, and an averaged DMcentroid was determined. The axis between the DMcentroid and the fovea was used to establish 12 30-degree sectors. Measurements from the DMcentroid to each clinician's DM (DMradius) and RM (RMradius) were used to generate a RW (DMradius-RMradius) and cup-to-disc ratio (CDR) (RMradius/DMradius) by sector. Parameter means, standard deviations, and coefficient of variations (COVs) were calculated across all clinicians for each eye. Parameter means for each clinician, and intraclass correlation coefficients (ICC), were calculated across all eyes by sector. RESULTS: Among all eyes, the median COV by sector ranged from 3% to 5% for DMradius, 20% to 25% for RMradius, and 26% to 30% for RW. Sectoral ICCs for CDR ranged from 0.566 to 0.668. Sectors suspicious for rim thinning by 1 clinician were frequently overlooked by others. Among 1724 sectors in which at least 1 clinician was suspicious for rim thinning (CDR ≥ 0.7), all 5 clinicians' CDRs were ≥ 0.7 in only 499 (29%), and 2 of the 5 clinicians failed to detect rim thinning (CDR < 0.7) in 442 (26%). CONCLUSION: In this study, glaucoma specialist RM, DM, and RW discordance was frequent and substantial, even in sectors that were suspicious for rim thinning.

Effect of Pilocarpine Hydrochloride on the Schlemm Canal in Healthy Eyes and Eyes With Open-Angle Glaucoma.

IMPORTANCE: The in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use. OBJECTIVE: To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 µm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES: Mean cross-sectional area of the Schlemm canal. RESULTS: Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] µm2) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] µm2) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) µm3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) µm3 in eyes with glaucoma (P < .001). CONCLUSIONS AND RELEVANCE: These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

Intracranial pressure (ICP) and optic nerve subarachnoid space pressure (ONSP) correlation in the optic nerve chamber: the Beijing Intracranial and Intraocular Pressure (iCOP) study.

PURPOSE: Because a lowered intracranial pressure (ICP) is a possible mechanism of optic neuropathy, we wished to study the CSF dynamics in the optic nerve chamber by recording possible changes in the optic nerve subarachnoid space pressure (ONSP) and the impact on it when acutely lowering ICP. METHODS: In eight normal dogs pressure probes were implanted in the left brain ventricle, lumbar cistern, optic nerve subarachnoid space and in the anterior eye chamber. Following CSF shunting from the brain ventricle we monitored changes of ICP, lumbar cistern pressure (LCP), ONSP and intraocular pressure (IOP). RESULTS: At baseline, the pressures were different with ICP>LCP>ONSP but correlated with each other (P<0.001). The "trans-lamina cribrosa pressure gradient" (TLPG) was highest for IOP-ONSP, lower for IOP-LCP, and lowest for IOP-ICP (P<0.001). During CSF shunting the ICP gradually decreased in a linear fashion together with the ONSP ("ICP-depended zone"). But when the ICP fell below a critical breakpoint, ICP and ONSP became uncoupled and ONSP remained constant despite further ICP decline ("ICP-independent zone"). CONCLUSIONS: Because the parallel decline of ICP and ONSP breaks down when ICP decreases below a critical breakpoint, we interpret this as a sign of CSF communication arrest between the intracranial and optic nerve SAS. This may be caused by obstructions of either CSF inflow through the optic canal or outflow into the intra-orbital cavity. This CSF exchange arrest may be a contributing factor to optic nerve damage and the optic nerve chamber syndrome which may influence the loss of vision or its restoration.

The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change.

PURPOSE: To characterize optic nerve head (ONH) connective tissue change within 21 monkey experimental glaucoma (EG) eyes, so as to identify its principal components. METHODS: Animals were imaged three to five times at baseline then every 2 weeks following chronic unilateral IOP elevation, and euthanized early through end-stage confocal scanning laser tomographic change. Optic nerve heads were serial-sectioned, three-dimensionally (3D) reconstructed, delineated, and quantified. Overall EG versus control eye differences were assessed by general estimating equations (GEE). Significant, animal-specific, EG eye change was required to exceed the maximum physiologic intereye differences in six healthy animals. RESULTS: Overall EG eye change was significant (P < 0.0026) and animal-specific EG eye change most frequent, for five phenomena (number of EG eyes and range of animal-specific change): posterior laminar deformation (21, -29 to -437 µm), laminar thickening (11, 20-73 µm) and thinning (3, -23 to -31 µm), scleral canal expansion (17, 20-139 µm), outward anterior (16, -16 to -124 µm) and posterior (17, -22 to -279 µm) laminar insertion migration, and peripapillary scleral bowing (11, 21-77 µm). Experimental glaucoma versus control eye laminar thickness differences were bimodal in behavior, being thickened in most EG eyes demonstrating the least deformation and less thickened or thinned in most EG eyes demonstrating the greatest deformation. CONCLUSIONS: Our postmortem studies retrospectively identify five connective tissue components of ONH "cupping" in monkey EG which serve as targets for longitudinally staging and phenotyping ONH connective tissue alteration within all forms of monkey and human optic neuropathy.

Clinical Signs and Characteristics of Exfoliation Syndrome and Exfoliative Glaucoma in Northern China.

PURPOSE: To investigate the frequency and clinical features of exfoliation syndrome (XFS) and exfoliative glaucoma (XFG) in northern China. DESIGN: A retrospective medical chart review. METHODS: The review was conducted in Beijing Tongren Hospital. Using diagnosis codes, all consecutive patients with XFS/XFG were included in the study. Exfoliation syndrome was diagnosed if the patient had exfoliationmaterial (XFM) on the pupillary margin or anterior lens capsule. RESULTS: Of 73,976 inpatient records, 45 patients (75 eyes) with XFS/XFG were identified (27 men, 18 women). Exfoliation syndrome/XFG accounted for 0.55% (45/8205) of hospitalized patients with cataract aged 60 years or older. The mean (SD) age of the inpatients was 72.1 (8.1) years (range, 47-85 years). Thirty-six patients had XFG, comprising 4.3% (36/838) of hospitalized patients with open-angle glaucoma. The presence of XFM on the pupillary margin (66.7%) and anterior lens surface (65.3%) were the most common features. Loss of pupillary ruff (13.3%) was uncommon. Increased pigmentation (49.3%) and flecks of XFM (9.3%) were seen on the trabecular meshwork, and 25 eyes (33.3%) had narrow angles. For those with bilateral XFS/XFG (66.7%, 30/45), 7 patients had bilateral XFS, 15 patients had bilateral XFG, and 8 patients had XFS in 1 eye but XFG in another eye. Twenty-two patients (44.4%) had hypertension, and 7 (15.6%) had ischemic heart diseases. CONCLUSIONS: Exfoliation syndrome/XFG is still uncommon in the northern Chinese population. Its major clinical characteristics are the deposit of XFM on the pupil rim or anterior lens surface and increased trabecular meshwork pigmentation.

Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys.

PURPOSE: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head. METHODS: This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys). At baseline and in monthly intervals thereafter, optical coherence tomographic and photographic images of the optic nerve head and RNFL were taken of all monkeys. RESULTS: Two out of four monkeys in the study group showed bilaterally a progressive reduction in RNFL thickness between 12% and 30%, reduction in neuroretinal rim area and volume, and increase in cup-to-disc area ratios. A third monkey developed a splinter-like disc hemorrhage in one eye. The fourth monkey in the study group did not develop morphologic changes during follow-up, nor did any monkey in the control group. CONCLUSIONS: Experimental and chronic reduction in CSF in monkeys was associated with the development of an optic neuropathy in some monkeys.

Anatomic vs. acquired image frame discordance in spectral domain optical coherence tomography minimum rim measurements.

PURPOSE: To quantify the effects of using the fovea to Bruch's membrane opening (FoBMO) axis as the nasal-temporal midline for 30° sectoral (clock-hour) spectral domain optical coherence tomography (SDOCT) optic nerve head (ONH) minimum rim width (MRW) and area (MRA) calculations. METHODS: The internal limiting membrane and BMO were delineated within 24 radial ONH B-scans in 222 eyes of 222 participants with ocular hypertension and glaucoma. For each eye the fovea was marked within the infrared reflectance image, the FoBMO angle (θ) relative to the acquired image frame (AIF) horizontal was calculated, the ONH was divided into 30° sectors using a FoBMO or AIF nasal/temporal axis, and SDOCT MRW and MRA were quantified within each FoBMO vs. AIF sector. For each sector, focal rim loss was calculated as the MRW and MRA gradients (i.e. the difference between the value for that sector and the one clockwise to it divided by 30°). Sectoral FoBMO vs. AIF discordance was calculated as the difference between the FoBMO and AIF values for each sector. Generalized estimating equations were used to predict the eyes and sectors of maximum FoBMO vs. AIF discordance. RESULTS: The mean FoBMO angle was -6.6±4.2° (range: -17° to +7°). FoBMO vs. AIF discordance in sectoral mean MRW and MRA was significant for 7 of 12 and 6 of 12 sectors, respectively (p<0.05, Wilcoxon test, Bonferroni correction). Eye-specific, FoBMO vs. AIF sectoral discordance was predicted by sectoral rim gradient (p<0.001) and FoBMO angle (p<0.001) and achieved maximum values of 83% for MRW and 101% for MRA. CONCLUSIONS: Using the FoBMO axis as the nasal-temporal axis to regionalize the ONH rather than a line parallel to the AIF horizontal axis significantly influences clock-hour SDOCT rim values. This effect is greatest in eyes with large FoBMO angles and sectors with focal rim loss.

Anterior lamina cribrosa surface depth, age, and visual field sensitivity in the Portland Progression Project.

PURPOSE: To assess the effect of age on spectral-domain optical coherence tomography (SDOCT)-detected lamina cribrosa depth while controlling for visual field (VF) status and retinal nerve fiber layer thickness (RNFLT) in 221 high-risk ocular hypertension and glaucoma patients enrolled in the Portland Progression Project. METHODS: In this cross-sectional study, each participant underwent 870-nm SDOCT to obtain high-resolution radial B-scans centered on the optic nerve head (ONH) and a standardized ophthalmologic examination, including automated perimetry, on the same day. For each ONH, an anterior lamina cribrosa surface depth (ALCSD) parameter was generated as the average perpendicular distance from each anterior lamina cribrosa surface point relative to Bruch's membrane opening (BMO) reference plane within all 24 delineated B-scans. The relative effects of age, age-corrected VF status (mean deviation [MD]), and RNFLT on ALCSD were analyzed. RESULTS: The mean age ± SD of participants was 64 ± 11 years (range, 33-90 years). The relationship between ALCSD and MD was age-dependent. ALCSD = 407.68 - 67.13 × MD - 0.08 × Age + 0.89 × MD × Age (MD, P = 0.001; MD × Age, P = 0.004). The relationship between ALCSD and RNFLT may also be age-dependent but did not achieve significance (interaction term, P = 0.067). ALCSD increased with worse VF status in younger eyes but not in older eyes. In older eyes, the anterior lamina was shallower than in younger eyes for the same VF status and RNFLT. CONCLUSIONS: These data are consistent with the concept that structure/structure and structure/function relationships change with age.

A method to estimate the amount of neuroretinal rim tissue in glaucoma: comparison with current methods for measuring rim area.

PURPOSE: To test whether the minimum rim area assessed by spectral domain optical coherence tomography (SD-OCT), based on the shortest distance from the Bruch membrane opening (BMO) to the inner limiting membrane, corresponds more closely to retinal nerve fiber layer (RNFL) thickness and visual field mean deviation (MD) than current rim measures in early glaucoma. DESIGN: Prospective cross-sectional study. METHODS: We studied 221 participants with non-endstage glaucoma or high-risk ocular hypertension and performed standard automated perimetry. We received SD-OCT and confocal scanning laser ophthalmoscopy (CSLO) scans on the same day. Rim area measured by CSLO was compared with 3 SD-OCT rim measures from radial B-scans: horizontal rim area between BMO and inner limiting membrane within the BMO plane; mean minimum rim width (BMO-MRW); and minimum rim area (BMO-MRA) optimized within sectors and then summed. Correlations between these measures and either MD from perimetry or RNFL thickness from SD-OCT were compared using the Steiger test. RESULTS: RNFL thickness was better correlated with BMO-MRA (r = 0.676) or BMO-MRW (r = 0.680) than with either CSLO rim area (r = 0.330, P < 0.001) or horizontal rim area (r = 0.482, P < 0.001). MD was better correlated with BMO-MRA (r = 0.534) or BMO-MRW (r = 0.546) than with either CSLO rim area (r = 0.321, P < 0.001) or horizontal rim area (0.403, P < 0.001). The correlation between MD and RNFL thickness was r = 0.646. CONCLUSIONS: Minimum rim measurements from SD-OCT are significantly better correlated to both RNFL thickness and MD than rim measurements within the BMO plane or based on the clinical disc margin. They provide new structural parameters for both diagnostic and research purposes in glaucoma.

Role of B lymphoma Mo-MLV insertion region 1 in the oncogenic behavior of retinoblastomas.

PURPOSE: This study investigated the relationship between B lymphoma Mo-MLV insertion region 1 (BMI-1)--a polycomb protein for stem cell self-renewal and proliferation--and the clinicopathological parameters of human retinoblastomas, including differentiation status and retinal tissue invasion, as well as the effects of BMI-1 on retinoblastoma Y79 cells. METHODS: Thirty-four archived human retinoblastoma samples were recruited for BMI-1 immunohistochemistry. The percentage of BMI-1-expressing cells was scored by independent pathologists and the data were correlated with the clinical features. Y79 cells were transfected to overexpress or specifically inhibit BMI-1 for cell proliferation, propidium iodide cell cycle and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis analyses, multicellular sphere formation assay, and gene expression study. RESULTS: BMI-1 was widely expressed in human retinoblastomas. Higher percentages of BMI-1-expressing cells were selectively limited to undifferentiated tumors and those tumors undergoing invasion to the optic nerve and choroid. However, there was no difference in BMI-1 expression in retinoblastoma retinas with or without tumor invasion. In Y79 cells, BMI-1 stimulated cell proliferation and suppressed apoptosis with reduced p14ARF and p16INK4 expression, along with upregulation of proliferating cell nuclear antigens cyclin D1 and D2. In contrast, silencing BMI-1 reversed these changes. It also upregulated CHX10 and Rx, but not other retinal development-related genes, including nestin and neurofilament M. CONCLUSIONS: Our work indicates that BMI-1 might render important oncogenic property of retinoblastomas and it could be a therapeutic target for the cancer treatment.

Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study.

OBJECTIVE: Low cerebrospinal fluid pressure (CSF-P) may be involved in the pathogenesis of glaucoma. We measured the optic nerve subarachnoid space width (ONSASW) as a surrogate for orbital CSF-P in patients with primary open-angle glaucoma (POAG) with normal and high pressure and a control group. DESIGN: Prospective observational study. PARTICIPANTS: The study included 39 patients with POAG; 21 patients had normal pressure (intraocular pressure [IOP] 21 mmHg), and 18 patients had high pressure (IOP >21 mmHg); 21 subjects formed the control group. METHODS: By using magnetic resonance imaging (MRI) with fat-suppressed fast recovery fast spin echo (FRFSE) T2-weighted sequence, we determined the ONSASW at 3, 9, and 15 mm posterior to the globe. MAIN OUTCOME MEASURES: The ONSASW and optic nerve diameter. RESULTS: At all 3 measurement locations of 3, 9, and 15 mm, the ONSASW was significantly (P<0.001, P<0.001, and P = 0.003, respectively) narrower in the normal-pressure group (0.67±0.16, 0.55±0.09, and 0.51±0.12 mm, respectively) than in the high-pressure group (0.93±0.21, 0.70±0.12, and 0.62±0.11 mm, respectively) or the control group (0.87±0.15, 0.67±0.07, and 0.61±0.07 mm, respectively). The high-pressure and control groups did not vary significantly at 3, 9, and 15 mm (P = 0.31, P = 0.39, and P = 0.44, respectively). At all 3 measurement locations, ONSASW was narrower in the normal-pressure group compared with the high-pressure and control groups after adjustment for optic nerve diameter (P<0.01). Correspondingly, the width of the optic nerve subarachnoid space measured at 3, 9, and 15 mm behind the globe, respectively, was significantly (all P<0.05) associated with IOP after adjustment for optic nerve diameter and visual field defect. CONCLUSIONS: The narrower orbital optic nerve subarachnoid space in patients with POAG with normal pressure compared with high pressure suggests a lower orbital CSF-P in patients with POAG with normal pressure.

Effects of matrine on proliferation and apoptosis of cultured retinoblastoma cells.

BACKGROUND: Extracted from the traditional Chinese medicine of Kushen, matrine is an alkaloid with potential anti-neoplastic and anti-inflammatory effects. Here, we examined the effect of matrine on proliferation and apoptosis of cultured retinoblastoma cells. METHODS: The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 were treated with matrine in increasing concentrations from 0.2-1.1 mg/ml for 24 hours, and the cell proliferation rate was measured. The cells were exposed to matrine at 50% inhibition concentration (IC50) for 12, 24 and 48 hours. Cell cycle was analyzed by flow cytometry, concentration of proteins regulating cell cycle and apoptosis was determined by Western blot, apoptosis rate was measured by TUNEL staining, and cell morphology was assessed by electron transmission microscopy. RESULTS: The retinoblastoma cell lines Y79, WERI-RB1 and SO-RB50 showed an increased inhibition of cell proliferation with increasing matrine concentrations. Applying the IC50 concentration of matrine, the alteration of the cell cycle, including a reduced percentage of the S phase, was significantly (P < 0.01) associated with a longer treatment time by matrine. Correspondingly, the cell-cycle-associated proteins P21 and P27 were up-regulated and the protein cyclinD1 was down-regulated. The apoptosis-associated protein Bcl-2 was down-regulated, and Bax was up-regulated. In a similar manner, the apoptosis rate was significantly increased with longer treatment time. CONCLUSIONS: Matrine added to cultures of immortalized retinoblastoma cells led to a reduced tumor cell proliferation, decreased rate of mitosis and an increased tumor cell apoptosis, paralleled by corresponding changes in the proteins regulating the cell cycle or apoptosis.

Trans-lamina cribrosa pressure difference correlated with neuroretinal rim area in glaucoma.

BACKGROUND: The aim of this work is to prospectively assess the relationship between trans-laminar cribrosa pressure difference and neuroretinal rim area as morphologic surrogate of glaucomatous optic nerve damage. METHODS: The study included 22 patients with high-pressure glaucoma, 13 patients with normal-pressure glaucoma, and 17 subjects with ocular hypertension. All participants underwent a standardized ophthalmologic examination including confocal laser scanning tomography of the optic nerve head and computerized perimetry and a neurologic examination including measurement of the lumbar cerebrospinal fluid (CSF) pressure. The trans-lamina cribrosa pressure difference was calculated as difference of intraocular pressure minus lumbar CSF pressure. RESULTS: Neuroretinal rim area (p = 0.006; correlation coefficient r = -0.38) and mean visual field defect (p = 0.008; r = 0.38) were significantly associated with trans-lamina cribrosa pressure difference. The probability of error was lower (i.e., the p value were lower) and the correlation coefficients were higher for the associations between rim area/visual field defect with trans-lamina cribrosa pressure difference than for the associations between rim area/visual field defect and intraocular pressure or lumbar CSF pressure. CONCLUSIONS: The trans-lamina cribrosa pressure difference as the difference of intraocular pressure minus the lumbar CSF pressure was the main pressure parameter associated with the amount of glaucomatous optic nerve damage. This may suggest that the CSF pressure as trans-lamina cribrosa counter pressure against the intraocular pressure may play some role in the pathogenesis of glaucomatous optic neuropathy.

Cerebrospinal fluid pressure in ocular hypertension.

BACKGROUND: To assess the lumbar cerebrospinal fluid pressure (CSF-P) in ocular hypertensive subjects with elevated intraocular pressure (IOP) but without development of glaucomatous optic nerve damage. METHODS: The prospective interventional study included 17 patients with ocular hypertension and 71 subjects of a nonglaucomatous control group. All patients underwent a standardized ophthalmologic and neurological examination including measurement of lumbar CSF-P. In the ocular hypertensive group, the IOP was corrected for its dependence on central corneal thickness (IOP(corrected) ). The trans-lamina cribrosa pressure difference (Trans-LCPD) was calculated as IOP(corrected) - CSF-P. RESULTS: CSF-P was significantly (p < 0.001) higher in the ocular hypertensive group (16.0 ± 2.5 mmHg) than in the control group (12.9 ± 1.9 mmHg). CSF-P was significantly associated with IOP(corrected) (p < 0.001; r = 0.82). In multivariate analysis, CSF-P was significantly correlated with IOP(corrected) (p < 0.001) and marginally significantly with mean blood pressure (p = 0.05). Trans-LCPD was not associated significantly with blood pressure (p = 0.69). CONCLUSION: Some ocular hypertensive subjects with increased intraocular pressure measurements (after correction for their dependence on central corneal thickness) had an abnormally high lumbar cerebrospinal fluid pressure. Assuming that lumbar cerebrospinal fluid pressure correlated with orbital cerebrospinal fluid pressure, one may postulate that the elevated retro-lamina cribrosa pressure compensated for an increased intraocular pressure. The elevated retro-lamina cribrosa pressure may have led to a normal trans-laminar pressure difference in the eyes with elevated intraocular pressure, so that glaucomatous optic nerve damage did not develop. Intraocular pressure, cerebrospinal fluid pressure and arterial blood pressure were correlated with each other.