Sergio H. Teixeira

Effect of Etidronate Treatment on Bone Mass of Male Nephrolithiasis Patients with Idiopathic Hypercalciuria and Osteopenia

Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 ± 1.0% (mean ± SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 ± 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 ± 1.0% and 2.0 ± 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 ± 2.2 vs. 12.2 ± 1.1%, 1.2 ± 0.7 vs. 2.6 ± 0.7%, and 20.7 ± 6.2 vs. 13.7 ± 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 ± 5.2 vs. 18.8 ± 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.

Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

PURPOSE To use the pupillary light reflex and polysomnography to evaluate the function of intrinsically photosensitive retinal ganglion cells (ipRGCs) and to correlate this function with structural damage in glaucoma. DESIGN Cross-sectional study. PARTICIPANTS A study was conducted on both eyes of 45 participants (32 patients with glaucoma and 13 healthy subjects). METHODS For the pupillary reflex evaluation, patients were tested in the dark using a Ganzfeld system (RETIport; Roland Consult, Brandenburg, Germany); pupil diameter was measured with an eye tracker system. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors, we used a 1-second 640-nm flash with a luminance of 250 cd/m(2). All of the subjects underwent polysomnography. Subjects underwent standard automated perimetry and optical coherence tomography (Cirrus HD-OCT; Carl Zeiss Meditec Inc, Dublin, CA). MAIN OUTCOME MEASURES Correlations between ipRGC activity, as measured by the pupillary light reflex, and polysomnography parameters, and correlations between retinal nerve fiber layer (RNFL) thickness and the pupillary light reflex and polysomnography parameters. RESULTS The mean patient ages in the healthy and glaucoma groups were 56.8±7.8 years and 61.5±11.6 years, respectively (P = 0.174). Patients with glaucoma had significantly lower average total sleep time, sleep efficiency, and minimum oxyhemoglobin saturation compared with the healthy subjects (P  = 0.008, P = 0.002, and P = 0.028, respectively). Patients with glaucoma had significantly higher arousal durations after falling asleep and more periodic limb movements (P = 0.002 and P = 0.045, respectively). There was an inverse correlation between the rapid eye movement latency and the peak of the pupillary response to the blue flash (P = 0.004). The total arousals were inversely correlated with the sustained blue flash response (P = 0.029). The RNFL thickness was associated with the peak and sustained responses to the blue flash (P  <  0.001 for both comparisons); however, RNFL thickness was only associated with the mean oxygen desaturation index among the polysomnography parameters (P = 0.023). CONCLUSIONS This study demonstrated that decreased ipRGC function caused by glaucoma affected pupillary response and sleep quality.

Vitamin D receptor gene polymorphism and bone mineral density in hypercalciuric calcium-stone-forming patients.

Reduced bone mineral density (BMD) and an increased risk of vertebral fracture have been reported in calcium-stone-forming (CSF) patients presenting with idiopathic hypercalciuria. We investigated the association between BsmI vitamin D receptor (VDR) polymorphism and BMD in 68 hypercalciuric CSF patients (35 males and 33 premenopausal females, mean age ± SD = 39 ± 10 years). BMD was measured at lumbar spine (L2–L4) and femur neck sites using dual energy X-ray absorptiometry. A 72-hour dietary record and a 24-hour urine sample were obtained from each patient to determine calcium intake and excretion. The allelic frequency found for the sample as a whole was 16% BB, 44% Bb and 40% bb. Mean BMD values did not significantly differ among BB, Bb and bb patients at L2–L4 (1.162 ± 0.10, 1.133 ± 0.11 and 1.194 ± 0.19 g/cm2, mean ± SD, respectively) or at neck sites (0.920 ± 0.11, 0.931 ± 0.15 and 0.982 ± 0.15 g/cm2, respectively). Calcium intake and excretion were also not significantly different among the three genotypes. Patients were then divided into two groups, normal BMD, T-score ≧–1 (n = 34) and low BMD, T-score <–1 (n = 34), to further evaluate the allele influence on previous bone loss. Despite a trend for a higher mean BMD at spine or neck sites for patients with one or two b alleles when compared to BB patients, the difference did not reach statistical significance. The distribution of BB, Bb and bb genotypes in the low-bone-mass group (15, 47 and 38%, respectively) was similar to that in the normal-bone-mass group (18, 41 and 14%, respectively). These data suggest that BsmI VDR polymorphism does not play an important role in the bone loss seen in hypercalciuric CSF patients.

Association between corneal biomechanical properties and optic nerve head morphology in newly diagnosed glaucoma patients

Background:  To investigate the association between corneal biomechanics and optic nerve head morphology in newly diagnosed primary open‐angle glaucoma patients.

A positive association between intrinsically photosensitive retinal ganglion cells and retinal nerve fiber layer thinning in glaucoma.

PURPOSE To assess the integrity of intrinsically photosensitive retinal ganglion cells (ipRGCs) using the pupillary light reflex in glaucoma patients. METHODS A cross-sectional study was conducted, including 76 eyes from 38 patients with primary open-angle glaucoma and 36 eyes from 18 control subjects. The patients were tested in the dark with light stimuli using the Ganzfeld system, and the pupil diameter was measured with the assistance of an eye tracker consisting of two infrared cameras fit to an eyeglass frame. To preferentially stimulate ipRGCs, we used a 1-second 470-nm flash with a luminance of 250 cd/m(2). To stimulate different retinal photoreceptors (cones and rods), we used a 1-second 630-nm flash with a luminance of 250 cd/m(2). Standard automated perimetry (SAP), matrix frequency-doubling technology (FDT), and high-definition optical coherence tomography (Cirrus HD-OCT) were also performed. The correlation between the ipRGC-mediated sustained response following the pupillary light reflex and the structural and functional changes in glaucoma patients was analyzed using generalized estimating equation. RESULTS An association was observed between the average retinal nerve fiber layer (RNFL) thickness, as measured by Cirrus HD-OCT, and the sustained pupillary response to the blue flash (P = 0.024). The severity of glaucoma, based on the mean deviation of SAP (Hodapp-Anderson-Parrish system), was also associated with the sustained response to the blue flash (P = 0.006). CONCLUSIONS This study showed a correlation between the mean RNFL thickness and the pupillary light response. A decrease in the number of ipRGCs is potentially related to the reduced RNFL thickness.

Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients.

PurposeTo investigate factors associated with changes in optic nerve head (ONH) topography after acute intraocular pressure (IOP) reduction in patients with primary open-angle glaucoma (POAG).MethodsUntreated POAG patients (IOP >21 mm Hg) were prospectively enrolled. Systemic and ocular information were collected, including central corneal thickness (CCT) and corneal hysteresis (CH). All patients underwent confocal scanning laser ophthalmoscopy and tonometry (Goldmann) before and 1 h after pharmacological IOP reduction. The mean of three measurements was considered for analysis. Changes in each ONH topographic parameter were assessed (one eye was randomly selected), and those that changed significantly were correlated with patients systemic and ocular characteristics.ResultsA total of 42 patients were included (mean age, 66.7±11.8 years). After a mean IOP reduction of 47.3±11.9%, significant changes were observed in cup area and volume, and in rim area and volume (P<0.01), but not in mean cup depth (P=0.80). Multiple regression analysis (controlling for baseline IOP and magnitude of IOP reduction) showed that CH (r2=0.17, P<0.01) and diabetes diagnosis (r2⩾0.21, P<0.01) were negatively correlated with the magnitude of changes in ONH parameters, whereas the cup-to-disc ratio was positively correlated (r2=0.30, P<0.01). Age, race, disc area, and CCT were not significant (P⩾0.12). Including all significant factors in a multivariable model, only the presence of diabetes remained significantly associated with all ONH parameters evaluated (P<0.01).ConclusionsDifferent systemic and ocular factors, such as diabetes, CH, and the relative size of the cup, seem to be associated with the magnitude of changes in ONH topography after acute IOP reduction in POAG patients. These associations partially explain the ONH changes observed in these patients and suggest that other factors are possibly implicated in an individual susceptibility to IOP.

Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

Patients with glaucoma showed to have higher daytime sleepiness measured by Epworth sleepiness scale. In addition, this symptom was associated with pupillary reflex and polysomnography parameters. These ipRGC functions might be impaired in patients with glaucoma, leading to worse quality of life.

Evaluation of Glaucomatous Damage via Functional Magnetic Resonance Imaging, and Correlations Thereof with Anatomical and Psychophysical Ocular Findings

Purpose To evaluate the functional magnetic resonance imaging (fMRI) response to binocular visual stimulation and the association thereof with structural ocular findings and psychophysical test results in patients with glaucoma, and controls. Methods Cross-sectional study. Participants underwent a complete ophthalmic examination, including Humphrey 24-2 visual field (VF) testing and optical coherence tomography. Binocular VF in each quadrant was determined using an integrated method. Patients with glaucoma were assigned to three subgroups: initial, asymmetrical and severe glaucoma. Regions of interest (ROIs) were determined anatomically. fMRI (3 T) was performed using a bilaterally presented polar angle stimulus, and the accompanying changes in blood oxygen level-dependent (BOLD) signals were obtained from the occipital poles and calcarine ROIs. We used generalized estimation equation models to compare anatomical and functional data between the groups. Results A total of 25 subjects were enrolled, of whom 17 had glaucoma and 8 were controls. Significant associations between quadrant binocular VF sensitivities and fMRI responses were found in the occipital pole ROIs (p = 0.033) and the calcarine ROIs (p = 0.045). In glaucoma severity subgroup analysis, retinal nerve fiber layer (RNFL) thickness was associated with the BOLD response of the calcarine and occipital pole ROIs (p = 0.002 and 0.026, respectively). The initial and asymmetrical glaucoma subgroups had similar binocular VF sensitivities and RNFL thicknesses, but distinct BOLD responses. Conclusions The response of the visual cortex to binocular stimulation was associated with binocular VF sensitivity. RNFL thickness was associated with the BOLD response of the calcarine and occipital pole ROIs.

The potential neuroprotective effects of weekly treatment with glatiramer acetate in diabetic patients after panretinal photocoagulation

Purpose Evaluation of the neuroprotective effect of weekly glatiramer acetate (GA) on retinal structure and function in diabetic patients who underwent panretinal photocoagulation (PRP). Patients and methods Patients with severe nonproliferative or early proliferative diabetic retinopathy and no previous laser treatment were randomly divided into two groups: (1) those who received four GA treatments and (2) those who received placebo treatment. The subcutaneous injections were administered 1 week prior to laser and weekly in the subsequent three sessions of PRP in both groups. All patients underwent a full ophthalmic examination (best-corrected logMAR visual acuity, slit lamp examination, applanation tonometry, fundus biomicroscopy and indirect fundus examination); functional examination (standard automated perimetry, electroretinography and frequency-doubling technology C-20 visual field) and anatomic examination (color photography, optical coherence tomography (OCT) and Heidelberg retinal tomography). The examinations were performed before the photocoagulation and repeated 1,3,6, and 12 months after treatment (in a double-masked manner). To compare the two groups, generalized estimating equation models were performed to account for the dependence between eyes of the same patient. Results Thirteen patients (23 eyes) were included in the study group and 13 patients (24 eyes) were included in the control group. OCT showed a statistically significant difference in retinal nerve fiber layer (RNFL) thickness in the inferior peripapillary region and average thickness with thinner measurements in the control group at 1-year post-PRP. Functional analysis demonstrated a difference between groups, but it did not reach statistical significance. Conclusion The results of this study suggest that weekly GA treatment has a potential neuro-protective effect on the RNFL following photocoagulation for diabetic retinopathy.

New adjustable suture technique for trabeculectomy

PURPOSE To describe an adjustable suture (AS) experimental model that allows for tightening, loosening and retightening of the suture tension in trabeculectomy. METHODS Standard trabeculectomy was performed in fifteen pig eyeballs. All pig eyes were tested twice: one test with conventional suture in both flaps corners (conventional suture group) and another test with a conventional suture at one corner and an adjustable suture in the other corner (AS group). The order in which each test was performed was defined by randomization. Intraocular pressure was measured at three time points: T1) when the knots were tightened; T2) when the AS was loosened or the conventional knot was removed; and T3) when the AS was retightened in the AS group or five minutes after the knot removal in the conventional suture group. RESULTS The mean Intraocular pressure was similar between the two groups at time point 1 (p=0.97). However, significant Intraocular pressure differences were found between eyes in the conventional and adjustable suture groups at time points 2 (12.6 ± 4.2 vs 16.3 ± 2.3 cmH₂O, respectively, p=0.006) and 3 (12.2 ± 4.0 vs 26.4 ± 1.7 cmH₂O, respectively; p=0.001). While the conventional technique allowed only Intraocular pressure reduction (following the knot removal; T2 and T3), the AS technique allowed both Intraocular pressure reduction (T2) and elevation (T3) through the management (loosening and retightening) of the suture. CONCLUSION This experimental model provides an effective noninvasive postoperative mechanism of suture tension adjustment.