Matthias Boehnke

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.

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.

Aqueous Humor and Serum Immunoblotting for Immunoglobulin Types G, A, M, and E in Cases of Human Ocular Toxoplasmosis

ABSTRACT The purpose of this study was to compare the local and systemic Toxoplasma-specific humoral immune responses in individuals with ocular toxoplasmosis (OT). To this end, paired aqueous humor and serum samples from 46 individuals with active OT and from 30 individuals without inflammatory eye disease (controls) were analyzed by immunoblotting for anti-Toxoplasma immunoglobulin G (IgG), IgA, IgM, and IgE directed against 20- to 120-kDa antigens. The presence in the aqueous humor of a unique band, or of at least three bands that were at least three times more intense in aqueous humor than in serum, was taken as evidence of local antibody production. IgG bands were detected in 98% of the aqueous humor samples, while IgA bands were detected in 76%, IgM bands were detected in 8%, and IgE bands were not detected in any. Evidence of local production of specific antibodies was found in 32 cases (70%) (IgG in 23 [50%]; IgA in 16 [35%]). In 10 instances (22%), routine laboratory tests were not indicative of OT. In 14 cases (30%), no local antibody production was detected by immunoblotting; 3 of these cases yielded evidence of local antibody production according to the Goldmann-Witmer coefficient. Local antibody production was revealed for 7 of the 30 controls (23%). Hence, the sensitivity of immunoblotting for IgG and IgA is 70%, and the specificity is 77%. We conclude that immunoblotting for local specific IgG and IgA supports the clinical diagnosis of OT in 70% of cases. In 22% of these, the diagnosis is not confirmed by other laboratory tests. Hence, immunoblotting increases the sensitivity of routine laboratory tests and should be considered for samples that register negative by such tests.

Experimental Ocular Toxoplasmosis in Naive and Primed Rabbits

Purpose: Investigations of the course of ocular toxoplasmosis and the influence of a host’s immunological status in an animal model would contribute to our understanding of the pathophysiology underlying this condition. In the current study, these aspects are addressed using naive and primed rabbits infected transvitreally with the non-cyst-forming BK strain of Toxoplasma gondii. Materials and Methods: Of 45 latex agglutination test-negative rabbits, 27 were infected subcutaneously with 5,000 Toxoplasma tachyzoites, and the ensuing infection treated by systemic administration of clindamycin for 20 days. Four of these rabbits died from generalized infection. The remaining 23 primed rabbits were then inoculated periretinally with a further 5,000 Toxoplasma tachyzoites, administered via the transvitreal route; the 18 naive rabbits were treated likewise. Results: All 18 naive and 21 of the 23 primed rabbits developed toxoplasmic retinochoroiditis. As regarded progression of the disease, dissemination of the condition (p = 0.0001), degree of vitreal infiltration (p = 0.0001) and incidence of retinal detachment (p < 0.05) were all more pronounced in the naive group. Despite treatment, 4 of the 18 (22%) naive rabbits died from generalized infection, as did 4 of the 27 (15%) subcutaneously infected ones (prior to periretinal infection). In the primed (secondarily infected) animal group, only moderate signs of systemic infection were manifested, and there were no fatalities. Conclusion: The high incidence (> 90%) of retinochoroiditis achieved even in primed animals, by introducing Toxoplasma tachyzoites via the transvitreal route, may reflect the maintenance of an intact uveovascular barrier during the early stages of the disease. The pattern of infection, in being restricted primarily to the retina, mimics the situation evinced in humans. Regarding propagation of the disease, the condition manifested in naive rabbits resembles that occurring in immunodeficient patients, whereas that evoked in primed animals corresponds to recurrence of infection in immunocompetent patients.

Leber's hereditary optic neuropathy mitochondrial DNA mutations in normal-tension glaucoma.

Abstract. Background: in Lebers hereditary optic neuropathy, increased optic nerve cupping has been reported by several authors. Recently, a mitochondrial DNA (mtDNA) mutation at nucleotide 11778 typically associated with Lebers hereditary optic neuropathy (LHON) was identified in a patient treated for glaucoma but lacking typical signs of LHON. The question arises: should all normal-tension glaucoma patients be further evaluated for LHON? Methods: we screened 54 unselected patients with normal-tension glaucoma (age range 20–96 years, 16 men and 38 women) for the primary mtDNA LHON mutations at nucleotides 3460, 11778 and 14484. Results: none of the patients harboured the mtDNA mutations at nucleotides 3460, 11778 or 14484 (95% confidence intervals for each mutation ranged from 0% to 5.3%). Conclusions: primary LHON mtDNA mutations are rare or absent in unselected normal-tension glaucoma patients. Therefore, unselected normal-tension glaucoma patients should not be screened for these mutations. It is probable that only normal-tension glaucoma patients with atypical features (rapid progression, early deep central scotoma, pallor of neuroretinal rim, elevated disc, peripapillary teleangiectasia) or a positive family history of visual loss compatible with a matrilinear transmission should be further evaluated.

Low rate shedding of HSV-1 DNA, but not of infectious virus from human donor corneae into culture media

Fluid samples derived from 451 organ cultured corneae were tested for the presence of HSV‐1 DNA after electroseparation and amplification for fragments of the glycoprotein D‐ and thymidine kinase‐encoding genes. Of the culture media, 134 were processed immediately after withdrawal (Group 1); 100 were stored at ambient temperature for 6 to 60 weeks (Group 2); 90 were stored at −8°C for 4 to 9 weeks (Group 3); and 127 were stored at −20°C for 2 to 30 weeks (Group 4). The degradation of human DNA (marker gene, betaglobin) under these different storage conditions and of human and HSV‐1 DNA as a sequential function of time at ambient temperature was gauged by the loss of a detectable signal for the respective component. Endothelial cell density within each of the corneal discs was determined before and after organ culture.

Effect of topical anesthetic agents and ethanol on corneoepithelial wound healing in an ex vivo whole-globe porcine model

PURPOSE: To assess the impact of topical anesthetic agents and ethanol on ocular surface wound healing using an ex vivo whole‐globe porcine model. SETTING: Department of Ophthalmology, Inselspital, University of Bern, Bern, Switzerland. DESIGN: Experimental study. METHODS: Standardized corneoepithelial lesions (5.0 mm diameter, 40 μm depth) were created with excimer laser light in freshly enucleated porcine eyes. The globes (6 per group) were exposed to different concentrations of ethanol (2.0% to 99.0%), cocaine (2.0% to 10.0%), procaine hydrochloride (0.4%), tetracaine (0.5% to 1.0%), or lidocaine (2.0%), 3 drops/hour for 3 hours. Control solutions were physiologic saline, balanced salt solution, and tissue‐culture medium. After 20 to 26 hours, wound‐healing response was compared by measuring the diameter of each corneoepithelial lesion. RESULTS: The mean diameter of corneoepithelial lesions exposed to physiologic saline decreased from 4.78 mm ± 0.19 (SD) to 4.44 ± 0.17 mm between 20 and 26 hours. After 24 hours, the mean lesion size, compared with physiological saline, was larger after cocaine 5.0% (5.20 ± 0.26 mm) and 10.0% (5.39 ± 0.12 mm), tetracaine 0.5% (5.59 ± 0.35 mm) and 1.0% (5.55 ± 0.27 mm), and procaine hydrochloride 0.4% (5.76 ± 0.12 mm), but not after lidocaine 2.0% (5.01 ± 0.17 mm). Balanced salt solution, tissue‐culture medium, ethanol 2.0% to 99.0%, and cocaine 2.0% did not inhibit the wound‐healing response. CONCLUSIONS: In an ex vivo whole‐globe porcine model, lidocaine 2.0% and cocaine 2.0% were the least toxic anesthetic agents. At all concentrations, ethanol had no impact on wound healing. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Book Review / Announcement

This second edition gives a very nice overview of the embryogenesis, organogenesis and differentiation of the eye and its adnexa. Ophthalmologists, pediatrics as well as students will make a large profit from this compendium. The early development of the anatomic structures is extremely well illustrated, newly acquired information from research is included. The reference sources are rich and also enable researchers a far-reaching survey. M. Lüchtenberger, Frankfurt