Ocular pulse amplitude in healthy subjects as measured by dynamic contour tonometry

OBJECTIVES: To test whether dynamic contour tonometry yields ocular pulse amplitude (OPA) measurements that are independent of corneal thickness and curvature, and to assess variables of observer agreement. METHODS: In a multivariate cluster analysis on 223 eyes, the relationship between central corneal thickness, corneal curvature, axial length, anterior chamber depth, intraocular pressure, sex, age, and OPA measurements was assessed. Intraobserver and interobserver variabilities were calculated from repeated measurements obtained from 8 volunteers by 4 observers. RESULTS: The OPA readings were not affected by central corneal thickness (P = .08), corneal curvature (P = .47), anterior chamber depth (P = .80), age (P = .60), or sex (P = .73). There was a positive correlation between OPA and intraocular pressure (0.12 mm Hg/1 mm Hg of intraocular pressure; P<.001) and a negative correlation between OPA and axial length (0.27 mm Hg/1 mm of length; P<.001). Intraobserver and interobserver variabilities were 0.08 and 0.02 mm Hg, respectively, and the intraclass correlation coefficient was 0.89. CONCLUSIONS: The OPA readings obtained with dynamic contour tonometry in healthy subjects are not influenced by the structure of the anterior segment of the eye but are affected by intraocular pressure and axial length. We found a high amount of agreement within and between observers.

Late-onset manifestation of antenatal Bartter syndrome as a result of residual function of the mutated renal Na+-K+-2Cl- co-transporter

Genetic defects of the Na+-K+-2Cl- (NKCC2) sodium potassium chloride co-transporter result in severe, prenatal-onset renal salt wasting accompanied by polyhydramnios, prematurity, and life-threatening hypovolemia of the neonate (antenatal Bartter syndrome or hyperprostaglandin E syndrome). Herein are described two brothers who presented with hyperuricemia, mild metabolic alkalosis, low serum potassium levels, and bilateral medullary nephrocalcinosis at the ages of 13 and 15 yr. Impaired function of sodium chloride reabsorption along the thick ascending limb of Henle's loop was deduced from a reduced increase in diuresis and urinary chloride excretion upon application of furosemide. Molecular genetic analysis revealed that the brothers were compound heterozygotes for mutations in the SLC12A1 gene coding for the NKCC2 co-transporter. Functional analysis of the mutated rat NKCC2 protein by tracer-flux assays after heterologous expression in Xenopus oocytes revealed significant residual transport activity of the NKCC2 p.F177Y mutant construct in contrast to no activity of the NKCC2-D918fs frameshift mutant construct. However, coexpression of the two mutants was not significantly different from that of NKCC2-F177Y alone or wild type. Membrane expression of NKCC2-F177Y as determined by luminometric surface quantification was not significantly different from wild-type protein, pointing to an intrinsic partial transport defect caused by the p.F177Y mutation. The partial function of NKCC2-F177Y, which is not negatively affected by NKCC2-D918fs, therefore explains a mild and late-onset phenotype and for the first time establishes a mild phenotype-associated SLC12A1 gene mutation.

Transient raise of endothelin-1 plasma level and reduction of ocular blood flow in a patient with optic neuritis

PURPOSE: To analyze how far an ischemic component might have been involved in optic neuritis. METHODS: Case report: a 32-year-old man with symptoms characteristic for optic neuritis underwent extensive clinical, laboratory/serological and vascular examination for systemic associations and vascular involvement. RESULTS: The patient was found to have a temporary ocular blood flow dysregulation and increased plasma endothelin-1 levels which decreased after the acute phase of the optic nerve. CONCLUSIONS: We conclude that there might be an ischemic component in this patient with optic neuritis and hypothesize that this ischemic component is at least in part due to a temporarily increased endothelin-1 level.

Influence of residual pockets on progression of periodontitis and tooth loss: results after 11 years of maintenance

BACKGROUND: Limited evidence exists on the significance of residual probing pocket depth (PPD) as a predictive parameter for periodontal disease progression and tooth loss. AIM: The aim of this study was to investigate the influence of residual PPD >or=5 mm and bleeding on probing (BOP) after active periodontal therapy (APT) on the progression of periodontitis and tooth loss. MATERIAL AND METHODS: In this retrospective cohort, 172 patients were examined after APT and supportive periodontal therapy (SPT) for 3-27 years (mean 11.3 years). Analyses were conducted using information at site, tooth and patient levels. The association of risk factors with tooth loss and progression of periodontitis was investigated using multilevel logistic regression analysis. RESULTS: The number of residual PPD increased during SPT. Compared with PPDor=7 mm 37.9 and 64.2, respectively. At patient level, heavy smoking, initial diagnosis, duration of SPT and PPD>or=6 mm were risk factors for disease progression, while PPD>or=6 mm and BOP>or=30% represented a risk for tooth loss. CONCLUSION: Residual PPD>or=6 mm represent an incomplete periodontal treatment outcome and require further therapy.

Nonpeptide somatostatin receptor agonists specifically target ocular neovascularization via the somatostatin type 2 receptor

PURPOSE: To define the molecular pharmacology underlying the antiangiogenic effects of nonpeptide imidazolidine-2,4-dione somatostatin receptor agonists (NISAs) and evaluate the efficacy of NISA in ocular versus systemic delivery routes in ocular disease models. METHODS: Functional inhibitory effects of the NISAs and the somatostatin peptide analogue octreotide were evaluated in vitro by chemotaxis, proliferation, and tube-formation assays. The oxygen-induced retinopathy (OIR) model and the laser model of choroidal neovascularization (CNV) were used to test the in vivo efficacy of NISAs. Transscleral permeability of a candidate NISA was also measured. RESULTS: NISAs inhibited growth factor-induced HREC proliferation, migration and tube formation with submicromolar potencies (IC(50), 0.1-1.0 microM) comparable to octreotide. In the OIR model, systemic administration of the NISAs RFE-007 and RFE-011 inhibited retinal neovascularization in a dose-dependent manner, comparable to octreotide. In the CNV model, intravitreal RFE-011 resulted in a 56% reduction (P < 0.01) in CNV lesion area, whereas systemic administration resulted in a 35% reduction (P < 0.05) in lesion area. RFE-011 demonstrated transscleral penetration. CONCLUSIONS: Micromolar concentrations of octreotide and NISAs are necessary for antiangiogenic effects, whereas nanomolar concentrations are effective for endocrine inhibition. This suggests that the antiangiogenic activity of NISAs and octreotide is mediated by an overall much less efficient downstream coupling mechanism than is growth hormone release. As a result, the intravitreal or transscleral route of administration should be seriously considered for future clinical studies of SSTR2 agonists used for treatment of ocular neovascularization to ensure efficacious concentrations in the target retinal and choroidal tissue.

Evaluation of secondary functional cheilorhinoplasty during growth of cleft patients with residual lip and nasal deformities

PURPOSE: The aim of the study was to evaluate the clinical outcomes of secondary functional cheilorhinoplasty of residual lip and nasal deformities caused by muscular deficiency in cleft patients. PATIENTS AND METHODS: During a 4-year period, 31 patients underwent cheilorhinoplasty, including complete reopening of the cleft borders and differentiated mimic muscle reorientation. In 21 patients, remarkable residual clefts of the anterior palate were also closed. Simultaneous alveolar bone grafting was performed in 15 patients. The minimum follow-up was 1 year. Cosmetic features evaluated were spontaneous facial appearance and changes in position of the nasal floor and the philtrum. The width of the alar base was measured. For functional outcomes, deficiency during mimic movements was evaluated, using standardized photographs taken preoperatively and postoperatively. The final results, judged according to defined criteria with several clinical factors, were compared. RESULTS: Cosmetic and functional improvement was achieved in all patients. In young patients (aged 4 to 9 years), the improvements were noteworthy. There were no differences in outcomes between the groups with and without simultaneous grafting, except for unilateral cases with minor muscular deficiency, in whom bone grafting before cheilorhinoplasty led to better results. CONCLUSION: In cases of major muscular deficiency, early cheilorhinoplasty should be performed at age 7 years, without waiting for the usual timing of bone grafting. In minor and moderate cases, the operation can ideally be done in combination with bone grafting.

Recurrence characteristics in European patients with ocular toxoplasmosis

BACKGROUND: The risk of function loss after each episode of ocular toxoplasmosis (OT) supports efforts to improve our understanding of the disease. Patients and methods: 139 patients with OT were contacted retrospectively and requested to complete a questionnaire addressing course and activity of their disease. This information was compared with that retrieved from their medical records. Sixty-three patients completed the questionnaire and were included in the study. They were allocated according to their median age to one of two groups (group 1: <20.9 years; group 2: >or=20.9 years). RESULTS: The mean reported age at the time of first ocular manifestation was 23.9 (median 20.9, range 0 to 70.5; SD 12.9) years. The clinical diagnosis was made 3.5 years later (p = 0.0008). The follow-up time was 6.5 (median 5.0; range 0.5 to 49.9; SD 7.6) years. The recurrence rate was higher in patients below 20.9 years (66%; n = 35) than in older patients (39%; n = 28; chi(2) test, p<0.05). Patients reporting only one episode were older at first manifestation (29.6 (median 25.6; range 10.6 to 70.5; SD 14.3) years; n = 29) than those reporting two episodes (17.9 (median 19.5; range 5.9 to 33.9; SD 7.8) years; n = 15 (p<0.05)). The proportion of patients who developed a recurrence was 54-63% after each episode without a tendency to enlarge, and the interval between successive episodes remained stable between 1.0 and 1.7 years for the first three recurrences. CONCLUSION: Younger OT patients carry a higher risk of developing a recurrence than older ones. After each episode, two-thirds of all OT patients will develop another one.

Abuse of vasoconstrictive eyedrops mimicking an ocular pemphigoid

To describe conjunctival histopathologic alterations induced by excessive chronic astringent use.

Residual oculomotor and exploratory deficits in patients with recovered hemineglect

Several studies on hemineglect have reported that patients recover remarkably well when assessed with neuropsychological screening tests, however, they show deficits on novel or complex tasks. We investigated whether such deficits can be revealed with eye movement analysis, applying two basic oculomotor tasks as well as two exploratory tasks. Eye movements were recorded in eight hemineglect patients at least eleven months after right-hemisphere brain damage had occurred. Sixteen healthy volunteers participated in the control group. Regarding the basic oculomotor tasks, only the overlap task revealed residual deficits in patients, suggesting that a directional deficit in disengaging attention persisted during recovery. Further residual deficits were evident in the exploratory tasks. When everyday scenes were explored, patients showed a bias in early orienting towards the ipsilateral hemispace. In a search task, they demonstrated the same orienting bias as well as a non-directional deficit concerning search times. Moreover, patients preferentially fixated in the contralateral hemispace, but did not benefit from this asymmetry in terms of search times, i.e. they did not detect contralateral targets faster than ipsilateral ones. This suggests a dissociation between oculomotor processes and attentional ones. In conclusion, we have identified behavioural aspects that seem to recover slower than others. A disengagement deficit and biases in early orienting have been the most pronounced residual oculomotor deficits.

Percutaneous PFO closure with Amplatzer PFO occluder: predictors of residual shunts at 6 months follow-up

OBJECTIVE: The objective of this study was to assess predictors of residual shunts after percutaneous patent foramen ovale (PFO) closure with Amplatzer PFO occluder (AGA Medical Corporation, Golden Valley, MN, USA). METHODS: All percutaneous PFO closures, using Amplatzer PFO occluder performed at a tertiary center between May 2002 and August 2006, were reviewed. Follow-up, including saline contrast transesophageal echocardiography, was performed in all patients 6 months after the intervention. PATIENTS: A total of 135 procedures were performed. Mean age of the patients was 51 years. The indication for PFO closure was an ischemic cerebrovascular event in 92%, paradoxical systemic embolism in 4%, and a diving accident in 4%. Recurrent events prior to PFO closure were noted in 34%. A concomitant atrial septal aneurysm was present in 61%. RESULTS: At 6 months follow-up, a residual shunt was detected in 26 patients (19%). Residual shunts were more common in patients with an atrial septal aneurysm (27 vs. 8%, P= .01) and in patients treated with a 35-mm compared with a 25-mm device (39 vs. 15%, P= .01). A concomitant atrial septal aneurysm remained independently associated with residual shunts when controlled for body mass index, gender, age, atrial dimensions, and presence of a Chiari network (odds ratio 4.1, 95% confidence intervals 1.1-15.0). CONCLUSION: The presence of atrial septal aneurysms in patients undergoing percutaneous PFO closure with an Amplatzer PFO occluder significantly increases the rate of residual shunts at 6 months follow-up, even if 35-mm devices are used.

New insights into ocular blood flow at very high altitudes

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.

BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterized by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor gene (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with (1) OFCD syndrome, (2) putative X-linked ('Lenz') microphthalmia syndrome, (3) isolated ocular defects and (4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.

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

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).