Eran Pras

Pacemaker endocarditis. Report of 44 cases and review of the literature.

We conducted a retrospective study to characterize the clinical course, microbiologic spectrum, and risk factors for endocarditis and for associated mortality in a large series of patients with documented pacemaker endocarditis. Using a computerized search through the medical records of 10 major hospitals in Israel from 1982 to 1992, and carefully reviewing the charts, we identified 44 patients with pacemaker endocarditis. The cases were categorized as definite (n = 25), probable (n = 12), or possible (n = 7) infective endocarditis based on strict case definition. Fever and chills were the most common symptoms. Increased ESR, leukocytosis, microscopic hematuria, and anemia were the most common laboratory findings. A relatively high proportion of the patients were diabetic. The most common source of endocarditis was infection acquired by the placement procedure or infection of the pacemaker pouch. Demographic, clinical, and laboratory features were similar to those of endocarditis patients of a similar age range without pacemakers, although the frequency of fever and chills was higher in our patients than in those patients and splenomegaly, vascular embolic phenomena, and new or changing murmurs were rare in our patients. The major pathogens were Staphylococcus aureus and Staphylococcus epidermidis, similar to other series of pacemaker-associated bacteremia and similar to the microbiologic findings of early prosthetic-valve endocarditis. However, this microbiologic profile is different from that of native-valve endocarditis. Although the present series did not show a statistically significant advantage to electrode removal over conservative treatment, when analyzed together with pooled data from other studies, it suggests that the surgical approach is preferable.(ABSTRACT TRUNCATED AT 250 WORDS)

Deleterious Mutations in the Zinc-Finger 469 Gene Cause Brittle Cornea Syndrome

Brittle cornea syndrome (BCS) is an autosomal-recessive disorder characterized by a thin cornea that tends to perforate, causing progressive visual loss and blindness. Additional systemic symptoms such as joint hypermotility, hyperlaxity of the skin, and kyphoscoliosis place BCS among the connective-tissue disorders. Previously, we assigned the disease gene to a 4.7 Mb interval on chromosome 16q24. In order to clone the BCS gene, we first narrowed the disease locus to a 2.8 Mb interval and systematically sequenced genes expressed in connective tissue in this chromosomal segment. We have identified two frameshift mutations in the Zinc-Finger 469 gene (ZNF469). In five unrelated patients of Tunisian Jewish ancestry, we found a 1 bp deletion at position 5943 (5943 delA), and in an inbred Palestinian family we detected a single-nucleotide deletion at position 9527 (9527 delG). The function of ZNF469 is unknown. However, a 30% homology to a number of collagens suggests that it could act as a transcription factor involved in the synthesis and/or organization of collagen fibers.

Mutations in FYCO1 Cause Autosomal-Recessive Congenital Cataracts

Congenital cataracts (CCs), responsible for about one-third of blindness in infants, are a major cause of vision loss in children worldwide. Autosomal-recessive congenital cataracts (arCC) form a clinically diverse and genetically heterogeneous group of disorders of the crystalline lens. To identify the genetic cause of arCC in consanguineous Pakistani families, we performed genome-wide linkage analysis and fine mapping and identified linkage to 3p21-p22 with a summed LOD score of 33.42. Mutations in the gene encoding FYVE and coiled-coil domain containing 1 (FYCO1), a PI(3)P-binding protein family member that is associated with the exterior of autophagosomes and mediates microtubule plus-end-directed vesicle transport, were identified in 12 Pakistani families and one Arab Israeli family in which arCC had previously been mapped to the overlapping CATC2 region. Nine different mutations were identified, including c.3755 delC (p.Ala1252AspfsX71), c.3858_3862dupGGAAT (p.Leu1288TrpfsX37), c.1045 C>T (p.Gln349X), c.2206C>T (p.Gln736X), c.2761C>T (p.Arg921X), c.2830C>T (p.Arg944X), c.3150+1 G>T, c.4127T>C (p.Leu1376Pro), and c.1546C>T (p.Gln516X). Fyco1 is expressed in the mouse embryonic and adult lens and peaks at P12d. Expressed mutant proteins p.Leu1288TrpfsX37 and p.Gln736X are truncated on immunoblots. Wild-type and p.L1376P FYCO1, the only missense mutant identified, migrate at the expected molecular mass. Both wild-type and p. Leu1376Pro FYCO1 proteins expressed in human lens epithelial cells partially colocalize to microtubules and are found adjacent to Golgi, but they primarily colocalize to autophagosomes. Thus, FYCO1 is involved in lens development and transparency in humans, and mutations in this gene are one of the most common causes of arCC in the Pakistani population.

Topical anesthesia using lidocaine gel for cataract surgery.

PURPOSE To assess the safety and efficacy of topical anesthesia using lidocaine gel in cataract surgery. SETTING Department of Ophthalmology, Meir Hospital, Sapir Medical Center, Kfar-Saba, Israel. METHODS One hundred cataract procedures (48 manual extracapsular cataract extraction [ECCE] and 52 phacoemulsification) were performed using lidocaine 2% gel as the sole anesthetic agent. The gel was applied 3 to 5 times prior to surgery. Intraoperative and postoperative data were recorded, and patients were asked to grade the pain on a scale of 0 (no pain) to 10 (unbearable pain). RESULTS Sixty-two percent of patients having manual ECCE and 74% having phacoemulsification reported no pain during surgery (score 0). The mean pain score in the manual ECCE group was 0.99 +/- 1.64 (SD); 3 patients required an additional intracameral lidocaine injection. The mean score in the phacoemulsification group was 0.72 +/- 1.47; no patient required additional anesthesia. CONCLUSIONS Topical application using lidocaine 2% gel is safe and highly effective, especially in clear corneal phacoemulsification. The gel also provides prolonged lubrication, further facilitating surgery.

Variations in corneal biomechanical parameters and central corneal thickness during the menstrual cycle

PURPOSE: To assess variations in the biomechanical properties and central corneal thickness (CCT) throughout the female menstrual cycle. SETTING: Department of Ophthalmology, Assaf Harofeh Medical Center, Zerifin Israel. DESIGN: Case series. METHODS: Young healthy women were prospectively recruited. Every participant was assessed at the beginning of the menstrual cycle, at ovulation, and at the end of the cycle. At every time point, corneal hysteresis (CH) and the corneal resistance factor (CRF) were measured with the Ocular Response Analyzer and the CCT was measured with an ultrasonic pachymeter. RESULTS: Twenty‐two eyes of 22 women (mean age 19.5 years ± 1.5 [SD]) were included. The CH was statistically significantly decreased at ovulation (10.1 mm Hg) compared with the beginning (11.1 mm Hg, P<.001) and the end (11.4 mm Hg, P<.001) of the cycle. The CRF was also significantly decreased at ovulation (9.8 mm Hg) compared with the beginning (10.6 mm Hg, P<.001) and the end (10.5 mm Hg, P<.001) of the cycle. The central cornea was thinnest at the beginning (535 μm) and statistically significantly thicker at ovulation (542 μm, P<.001) and at the end of the menstrual cycle (543 μm, P<.001). CONCLUSIONS: The CCT and biomechanical parameters significantly varied during the menstrual cycle. The CH and CRF were temporarily decreased at ovulation. The cornea was thinnest at the beginning and thicker at ovulation and at the end of the cycle. Such corneal changes may be important to consider during screening of candidates for laser refractive surgery. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned.

Treatment of a retinal dystrophy, fundus albipunctatus, with oral 9-cis-β-carotene

Background Fundus albipunctatus is a retinal dystrophy caused by a mutation in the gene encoding 11-cis-retinol dehydrogenase which delays the recovery of rod photoreceptor cells from light stimulation leading to night blindness. A recent study of a mouse model of fundus albipunctatus treated with 9-cis-retinal showed an improvement in visual function and structure. Methods Seven patients with fundus albipunctatus were given a daily food supplement of four capsules containing high-dose 9-cis-β-carotene for 90 days. The subjects were tested before and after treatment by visual field and electroretinogram in both eyes. This non-randomised prospective phase I study was registered at http://www.clinicaltrials.gov (NCT00478530). Results All patients showed significant improvements in peripheral visual field (mean deviation improved from −4.77±2.0 to −3.28±2.28, p=0.009, t test) and a highly significant improvement in rod recovery rates measured electroretinographically (maximal scotopic b-wave amplitude responses, improved from 197±49 μV to 292±48 μV, p<0.001, t test). No complications or side effects were observed. Conclusion Oral treatment with 9-cis-β-carotene led to reversal of a human retinal dystrophy. This potential therapy is readily available and should be evaluated in retinal dystrophies of similar mechanisms such as various types of retinitis pigmentosa.

Ocular parameters as an objective tool for the assessment of truck drivers fatigue

Ocular parameters are influenced by sleep derivation and the use of chemical substances which are two major causes for traffic accidents. We assessed the use of these parameters as an objective screening tool for a drivers fitness for duty. Pupillary diameter, pupil reaction to light and saccadic velocity were measured in 29 army truck drivers every morning for two months and compared to baseline measurements taken while the subjects were alert. An index which expressed the difference between study and baseline measurements was calculated, and drivers with significant deviation from baseline were disqualified and interviewed. Non-disqualified drivers served as controls. Twenty-nine percent of disqualified drivers reported sleeping less than the minimum of 7h required by army regulations compared with 8% of control drivers (p=0.01). Disqualified drivers had worse sleep quality the night before the test (Groningen Sleep Quality Scale, p=0.03) and incurred more accidents per driving day during their service (0.023 vs. 0.015 accidents/day, p=0.03). Two disqualified drivers admitted to using alcohol or sleeping pills. Thus, these ocular parameters may serve as a screening tool for drivers that are at high risk for driving. Drivers who were disqualified even once, tend to be involved in more motor vehicle accidents than their peers.

The Effects of Sleep Deprivation on Oculomotor Responses

Purpose: Fatigue due to sleep deprivation is one of the main causes of accidents. An objective and efficient method for determining whether the person is tired could provide a valuable tool in accident prevention. In this study, we evaluated whether oculomotor responses related to pupillary light reflex and saccadic velocity can identify subjects with sleep deprivation and whether these objective values correlate with subjective feeling of sleepiness. Methods: Thirteen normal subjects (5 male, 8 female) participated in a 4-day study. During the first two days following a full night’s (8 hr in bed) sleep, they underwent baseline automated oculomotor testing using the FIT-2500-Fatigue-Analyzer. Following a third full night’s sleep, participants were then sleep-deprived for 28 hr. Ten measurements of automated oculomotor tests were performed during the sleep deprivation period. Visually-guided saccadic velocity (SV), initial pupil diameter (PD), pupillary constriction latency (CL), and amplitude of pupil constriction (CA) were assessed using the FIT-2500-Fatigue-Analyzer. The FIT-index, which expresses the deviation of the ocular parameters from the baseline measurements, was calculated. Correlation of oculomotor parameters with the subjective Stanford Sleepiness Scale (SSS) was performed. Results: We found that oculomotor measures showed a significant increase in CL (298.6 to 308.4 msec, P < 0.05) and calculated FIT index (3.4 to 16.8, P < 0.05) and a significant decrease in SV (64.8 to 59.6 deg/sec) during sleep deprivation. The SSS was found to significantly increase over the sleep deprivation period (2.05 to 5.05, P < 0.05) and was significantly correlated with the FIT-index (r > 0.66, P < 0.02). Conclusion: Evaluation of oculomotor responses, particularly CL and SV together with the FIT-index, might have practical applications for the assessment of an individual’s state of alertness or fatigue. Correlation of the FIT-index to the SSS provides evidence for the potential usefulness of oculomotor function measurements in the detection of subjective sleepiness.

Correlation between asthenopic symptoms and different measurements of convergence and reading comprehension and saccadic fixation eye movements.

PURPOSE The aim of this study was to evaluate the relationship between asthenopic symptoms, convergence amplitude, reading comprehension, and saccadic eye movements in children 8 to 10 years of age. METHODS Sixty-six children age 8 to 10 years were examined. Convergence was evaluated using (1) nonaccommodative target at near and distance, (2) a near computerized stereogram, and (3) measurement of the near point of convergence (NPC). Reading ability was examined by (1) a reading comprehension test in which children had to answer questions regarding a paragraph they read and (2) the Developmental Eye Movement Test (DEM), which evaluates saccadic speed and accuracy. Asthenopic symptoms were scored by an Asthenopic Symptoms Questionnaire. RESULTS Asthenopic symptoms score was correlated with the near point of convergence (r = -0.4; P = 0.003), convergence on a near stereogram (r = 0.38; P = 0.01) and distant light (r = 0.27; P = 0.04), but not with convergence on a near nonaccommodative target (r = 0.07; P = 0.6). The DEM ratio score was correlated with the asthenopic symptoms score (r = -0.32; P = 0.01), but the reading comprehension test score was not (r = 0.12; P = 0.4). There was correlation, however, between the time for completion of the reading comprehension test and the asthenopic symptoms score (r = 0.39; P = 0.006). CONCLUSION Asthenopic symptoms score was correlated with convergence amplitude as measured, whereas accommodation is controlled and the ratio score calculated based upon DEM results. Further study is needed to evaluate the usefulness of the integration between symptom survey and objective reading examinations as screening tool for the diagnosis of convergence insufficiency.

Reversal of cystoid macular edema in gyrate atrophy patients

ABSTRACT Purpose: This study reports the presentation of two families with gyrate atrophy (GA). The aim of this study was to characterize the potential effect of therapeutic regimens on macular edema. Methods: Two unrelated patients with GA were studied for the potential effect of low protein diet (≤ 0.8 g/kg/d), and oral administration of pyridoxine (500 mg/day), on serum ornithine levels, best corrected visual acuity (BCVA), slit-lamp, OCT, and auto-fluorescence findings. Blood samples for DNA, mRNA, and exons of the OAT gene were screened for mutations and splicing effect when relevant. Results: At presentation, both patients manifested typical ophthalmic features of GA including cystoid macular edema (CME). One patient also exhibited optic nerve head hamartoma. Following treatment ornithine levels have lessened, BCVA improved, and central macular thickness (CMT) markedly decreased in all four studied eyes. The molecular pathologic features included a novel splice site mutation (c.900+1G>A). Conclusions: We have identified a novel mutation and two formerly described mutations in patients with GA. Of them, one patient comprised an unusual phenotype including bilateral astrocytic hamartomas. We have recognized for the first time improvement in CME following treatment with low protein intake and pyridoxine supplement. This finding may have significance in the understanding of treatment options for macular edema regardless of underlying etiology.