David Goldblum

High prevalence of glaucoma in patients with sleep apnea syndrome.

OBJECTIVE To determine the prevalence of glaucoma in sleep apnea syndrome (SAS), an entity characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurologic sequelae. DESIGN Cross-sectional study. PARTICIPANTS A total of 114 white patients consecutively referred for polysomnographic evaluation of suspected SAS. INTERVENTION Complete ophthalmologic examination, including computerized perimetry and simultaneous stereoscopic optic disc photographs. MAIN OUTCOME MEASURES Spearman rank correlations between the respiratory disturbance index during night sleep (RDI), a value used to diagnose and grade SAS, and visual acuity, intraocular pressure (IOP), visual field indices, presence or absence of glaucomatous optic disc changes, and diagnosis of glaucoma. Each correlation was controlled for age and body mass index. To compare proportions of patients harboring glaucoma, the binomial test was used. RESULTS Sixty-nine (60.5%) of the 114 patients had an RDI > or =10, which indicates SAS. Three patients had primary open-angle glaucoma, and two had normal-tension glaucoma. All patients with glaucoma had SAS. The observed prevalence of glaucoma in patients with SAS (5 of 69, 7.2%) was significantly higher than expected in a white population (2%) (P = 0.01). The RDI correlated positively with IOP (P = 0.025), visual field loss variance (P = 0.03), glaucomatous optic disc changes (P = 0.001), and diagnosis of glaucoma (P = 0.01). CONCLUSIONS Patients with SAS constitute a high-risk population for glaucoma and should therefore be screened for glaucoma.

Prospects for relevant glaucoma models with retinal ganglion cell damage in the rodent eye

Retinal ganglion cell (RGC) death is the end result of practically all diseases of the optic nerve, including glaucomatous optic neuropathy. Understanding the factors determining susceptibility of the retina or the optic nerve to glaucomatous damage, and the means to prevent it, requires good animal models. Here we review the different, current models in rodents that have been used to study RGC damage, discuss their value, and their adequacy as models for human glaucoma.

Comparison and evaluation of ocular biometry using a new noncontact optical low-coherence reflectometer.

PURPOSE To evaluate a new high-resolution noncontact biometer (Lenstar; Haag-Streit AG, Koeniz, Switzerland) using optical low-coherence reflectometry and to compare the clinical measurements with those obtained from the IOLMaster (Carl Zeiss, Jena, Germany) and the Pachmumeter (Haag-Streit AG). DESIGN Exploratory evaluation of diagnostic technology and nonrandomized, prospective clinical trial. PARTICIPANTS Eighty subjects (144 eyes) aged 20 to 90 years with cataractous, pseudophakic, aphakic, silicon oil-filled, or normal eyes. METHODS Measurements of axial length (AL), anterior chamber depth (ACD), central corneal thickness (CCT), corneal radius (R1 [flattest radius of corneal curvature] and R2 [steep radius, 90 degrees apart from R1]), and axis of the flattest radius (Ax1) obtained with the Lenstar were compared with those obtained with the IOLMaster or Pachmumeter. The results were evaluated using Bland-Altman analyses. The differences between both methods were assessed using the paired t test, and its correlation was evaluated by Pearson coefficient. MAIN OUTCOME MEASURES Axial length, CCT, ACD, R1, R2, and Ax1. RESULTS The overall mean AL measured with the Lenstar and the IOLMaster was 24.1 mm (r = 0.999). Anterior chamber depth was 3.19 mm (Lenstar) and 3.17 mm (IOLMaster; r = 0.875). Excellent correlations also were found for the corneal radius and the axis of flattest radius (R1, r = 0.927; R2, r = 0.929; and Ax1, r = 0.938). Mean CCT was 0.557 mm (r = 0.978) for both Lenstar and Pachmumeter. CONCLUSIONS Measurements with the new Lenstar correlated well with those with the IOLMaster and Pachmumeter in cataractous, pseudophakic, aphakic, silicon oil-filled, and normal eyes. It is an accurate, fast instrument that provides additional information of interest to any cataract or refractive surgeon.

Normal-tension glaucoma is associated with sleep apnea syndrome

Introduction: In normal-tension glaucoma, optic nerve damage occurs without elevated intraocular pressures, hence vascular and pathogenic mechanisms other than intraocular pressure effects have been postulated. However, the exact cause(s) remain unknown. We have looked for an association between normal-tension glaucoma and sleep apnea syndrome, a disease characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of late cardiovascular and neurological sequelae. Methods: We performed overnight polysomnography in 16 consecutive Caucasian patients with normal-tension glaucoma. The respiratory disturbance index (RDI) during night sleep was used to diagnose and grade obstructive sleep apnea. Patients with an RDI of 10 or more were diagnosed as having obstructive sleep apnea. Results: We observed the following prevalences of obstructive sleep apnea in normal-tension glaucoma patients: 0% (0 of 2) for the group of patients younger than 45 years, 50% (3 of 6) for the age group 45–64 years, and 63% (5 of 8) for the group older than 64 years. Prevalences in the middle and older age group were significantly higher than in a historic control group (p < 0.025 for both, binomial test). Conclusion: Normal-tension glaucoma patients constitute a high-risk population for sleep apnea syndrome. Therefore, they should be screened for sleep apnea syndrome, and, if necessary, be treated to avoid late cardiovascular and neurological sequelae.

Primary open-angle glaucoma is associated with sleep apnea syndrome.

Introduction: The etiology of primary open-angle glaucoma remains unclear. Various risk factors, including vascular abnormalities, have been associated with this disease. Sleep-associated diseases, like sleep apnea syndrome, might also represent a risk factor. Sleep apnea syndrome is characterized by repetitive upper airway obstructions during sleep, inducing hypoxia and sleep disruption with the risk of cardiovascular and neurological sequelae. In this study, we determined the prevalence of sleep apnea syndrome in primary open-angle glaucoma patients. Methods: Overnight transcutaneous finger oximetry was performed in 30 consecutive patients having primary open-angle glaucoma. We assessed the oximetry disturbance index during night sleep, a parameter used to diagnose sleep apnea syndrome and to grade its severity. Results: Sleep apnea syndrome was more prevalent among primary open-angle glaucoma patients compared to normal historic controls of the same age and sex distribution (χ2 = 9.35, d.f. = 3, p < 0.025). The oximetry disturbance index grade was significantly larger in the primary open-angle glaucoma group compared to normal controls (U = 3,352, p = 0.01). According to the oximetry disturbance index, 20% (6/30) of primary open-angle glaucoma patients had sleep apnea syndrome. Conclusion: Primary open-angle glaucoma is associated with sleep apnea syndrome. Early recognition and treatment of sleep apnea syndrome are important to avoid cardiovascular and neurological complications.

Comparison of rebound tonometry with Goldmann applanation tonometry and correlation with central corneal thickness

Background/aims: Rebound tonometry (RT) is performed without anaesthesia with a hand held device. The primary aim was to compare RT with Goldmann applanation tonometry (GAT) and to correlate with central corneal thickness (CCT). The secondary aim was to prove tolerability and practicability of RT under “study conditions” and “routine practice conditions.” Methods: In group 1 (52 eyes/28 patients), all measurements were taken by the same physician, in the same room and order: non-contact optical pachymetry, RT, slit lamp inspection, GAT. Patients were questioned about discomfort or pain. In group 2 (49 eyes/27 patients), tonometry was performed by three other physicians during routine examinations. Results: RT was well tolerated and safe. Intraocular pressure (IOP) ranged between 6 mm Hg and 48 mm Hg. No different trends were found between the groups. RT tended to give slightly higher readings: n = 101, mean difference 1.0 (SD 2.17) mm Hg; 84.1% of RT readings within plus or minus 3 mm Hg of GAT; 95% confidence interval in the Bland-Altman analysis −3.2 mm Hg to +5.2 mm Hg. Both RT and GAT showed a weak positive correlation with CCT (r2 0.028 and 0.025, respectively). Conclusions: RT can be considered a reliable alternative for clinical screening and in cases where positioning of the head at the slit lamp is impossible or topical preparations are to be avoided.

Eyelid, conjunctival, and corneal findings in sleep apnea syndrome

OBJECTIVE To determine the prevalence of eyelid, conjunctival, and corneal findings in patients with sleep apnea syndrome (SAS). DESIGN Case series. PARTICIPANTS Seventy-two white patients referred for evaluation of suspected SAS. INTERVENTION Complete examination of eyelids, conjunctiva, and cornea, including videokeratography. MAIN OUTCOME MEASURES Spearman rank correlations were determined between the respiratory disturbance index (RDI) during night sleep, a value used to diagnose and grade SAS, and tear film break-up time, eyelid distraction distance, presence or absence of ocular irritation symptoms, blepharoptosis, floppy eyelids, lacrimal gland prolapse, keratoconus, and endothelial dystrophy. Each correlation was controlled for age and body mass index. RESULTS According to the RDI, 44 (61 %) of the 72 patients had SAS. The RDI correlated positively with the eyelid distraction distance (P = 0.05), presence or absence of floppy eyelids (P = 0.01), and lacrimal gland prolapse (P = 0.01), and correlated negatively with tear film break-up time (P = 0.02). None of our patients with floppy eyelids had corneal abnormalities. One patient with SAS had bilateral keratoconus; another had bilateral Fuch endothelial dystrophy. CONCLUSIONS Sleep apnea syndrome was significantly associated with reduced tear film break-up time, floppy eyelids, and lacrimal gland prolapse. However, ocular irritation symptoms and corneal involvement were rare among patients with SAS. These findings do not confirm previous studies that reported a high prevalence of corneal involvement in floppy eyelid syndrome.

Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

ABSTRACT Little is known about the ocular penetration of amphotericin B (AMB) and its lipid formulations, the current drug of choice in fungal endophthalmitis. The ocular distribution of AMB lipid complex (ABLC), liposomal AMB (L-AMB), and AMB deoxycholate (D-AMB) was studied in a rabbit model. D-AMB (1 mg/kg of body weight/day), ABLC (5 mg/kg/day), or L-AMB (5 mg/kg/day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 consecutive days after induction of unilateral uveitis by intravitreal injection of endotoxin. AMB concentrations in aqueous humor, vitreous humor, and plasma were determined by high-pressure liquid chromatography 16 h after administration of a single dose or 24 h after the last of seven doses. After single-dose administration, L-AMB achieved at least eightfold-higher AMB concentrations in the aqueous of inflamed eyes than ABLC or D-AMB (1.21 ± 0.58 μg/ml versus 0.14 ± 0.04 and 0.11 ± 0.09 μg/ml, respectively). At that time point no drug was detectable in the vitreous. After 7 days of treatment, the concentration of AMB in the vitreous was higher after treatment with L-AMB (0.47 ± 0.21 μg/ml) than after treatment with ABLC (0.27 ± 0.18 μg/ml) and D-AMB (0.16 ± 0.04 μg/ml). Similarly, AMB concentration in the aqueous was higher after repeated doses of L-AMB (0.73 ± 0.43 μg/ml) than after repeated doses of ABLC (0.03 ± 0.02 μg/ml) or D-AMB (0.13 ± 0.06 μg/ml). No AMB was detected in noninflamed eyes. Following systemic administration, AMB distribution to the eye is inflammation dependent and occurs sequentially, first to the aqueous and then to the vitreous. Compared to D-AMB and ABLC, L-AMB reaches higher drug concentrations in both ocular compartments.

Distribution of amyloid precursor protein and amyloid-beta in ocular hypertensive C57BL/6 mouse eyes

Purpose: Amyloid precursor protein (APP) and amyloid-beta (Aβ) appear to participate in the pathophysiology of retinal ganglion cell (RGC) death in glaucoma. We, therefore, determined the distribution of APP and Aβ in the retinas of C57BL/6 mice after induction of chronic ocular hypertension. Methods: Ocular hypertension was induced in one eye of three-month-old C57BL/6 mice by injection of hypertonic saline into episcleral veins. After 6 weeks of documented elevated intraocular pressure (IOP), retinas were fixed with 4% paraformaldehyde and processed for immunohistochemistry with antibodies including a polyclonal antibody to the C-terminus of Aβ 40 (Novartis 17-40/23) and a polyclonal antibody to the APP ectodomain (Novartis 474). Distribution and semiquantitative expression of APP and Aβ immunolabeling in ocular hypertensive and control retinas were graded in a masked fashion and compared. Results: APP and Aβ immunoreactivity was found in the pia/dura, optic nerve (ON), and RGC layer of ocular hypertensive retinas, whereas APP and Aβ immunoreactivity in the contralateral control eyes was detected only in the pia/dura. Comparison of ocular hypertensive and control eyes for Aβ immunolabeling was significant in the ON and RGC layer (p < 0.05) whereas no significant difference was found when compared for APP staining. Conclusions: High Aβ and APP levels were seen in ocular hypertensive retinas, probably due to abnormal APP-splicing in the presence of elevated IOP.

Topical Caspofungin for Treatment of Keratitis Caused by Candida albicans in a Rabbit Model

ABSTRACT Candida albicans is the most frequent cause of fungal keratitis in temperate regions. Caspofungin has potent activity against Candida spp. in a variety of clinical settings. Little is known, however, about its activity against fungal keratitis. We compared the efficacy of topical caspofungin with that of topical amphotericin B (AMB) in a rabbit model of experimental keratomycosis. Keratitis was induced with a standardized inoculum of Candida albicans (SC 5314) placed on the debrided cornea. Twenty-four hours after infection, animals were randomly assigned to treatment with 0.15% caspofungin, 0.5% caspofungin, 0.15% AMB, and a saline control (n = 12 rabbits in each group). For the first 12 h, treatment was repeated every 30 min and, after a 12-h pause, was resumed at hourly intervals for another 12 h. The animals were examined and killed 12 h after administration of the last dose. Treatment effects were evaluated by clinical assessment, fungal culture, and histopathology. Drug treatment significantly reduced corneal fungal recovery from 3.78 log10 CFU in saline-treated animals to 2.97, 1.76, and 1.18 log10 CFU in animals treated with 0.15% caspofungin, 0.5% caspofungin, and 0.15% AMB, respectively. By histopathology, the mean hyphal density was significantly lower in the corneas of treated animals than in those of the controls; there was no difference in hyphal densities between the different treatment groups. The depth of corneal invasion was not significantly reduced by the antifungal treatments. By clinical assessment, keratitis progressed in animals treated with saline, whereas disease progression was inhibited by all drug treatment regimens. In our rabbit model, 0.5% caspofungin was as effective as 0.15% AMB for the topical treatment of Candida keratitis. The potential clinical efficacy of caspofungin awaits further investigation.