Chaim Stolovitch

Outbreak of Life-Threatening Thiamine Deficiency in Infants in Israel Caused by a Defective Soy-Based Formula

Objective. Between October and November 2003, several infants with encephalopathy were hospitalized in pediatric intensive care units in Israel. Two died of cardiomyopathy. Analysis of the accumulated data showed that all had been fed the same brand of soy-based formula (Remedia Super Soya 1), specifically manufactured for the Israeli market. The source was identified on November 6, 2003, when a 5.5-month-old infant was admitted to Sourasky Medical Center with upbeat nystagmus, ophthalmoplegia, and vomiting. Wernickes encephalopathy was suspected, and treatment with supplementary thiamine was started. His condition improved within hours. Detailed history revealed that the infant was being fed the same formula, raising suspicions that it was deficient in thiamine. The formula was tested by the Israeli public health authorities, and the thiamine level was found to be undetectable (<0.5 μg/g). The product was pulled from the shelves, and the public was alerted. Thiamine deficiency in infants is very rare in developed countries. The aim of this study was to report the epidemiology of the outbreak and to describe the diagnosis, clinical course, and outcome of 9 affected infants in our care. Methods. After the index case, an additional 8 infants were identified in our centers by medical history, physical examination, and laboratory testing. The group consisted of 6 male and 3 female infants aged 2 to 12 months. All were assessed with the erythrocyte transketolase activity assay, wherein the extent of thiamine deficiency is expressed in percentage stimulation compared with baseline (thiamine pyrophosphate effect [TPPE]). Normal values range from 0% to 15%; a value of 15% to 25% indicates thiamine deficiency, and >25% indicates severe deficiency. Blood lactate levels (normal: 0.5–2 mmol/L) were measured in 6 infants, cerebrospinal fluid lactate in 2 (normal: 0.5–2 mmol/L), and blood pyruvate in 4 (normal: 0.03–0.08 mmol/L). The diagnostic criteria for thiamine deficiency were abnormal transketolase activity and/or unexplained lactic acidosis. Treatment consisted of intramuscular thiamine 50 mg/day for 14 days combined with a switch to another infant formula. Results. Early symptoms were nonspecific and included mainly vomiting (n = 8), lethargy (n = 7), irritability (n = 5), abdominal distension (n = 4), diarrhea (n = 4), respiratory symptoms (n = 4), developmental delay (n = 3), and failure to thrive (n = 2). Infection was found in all cases. Six infants were admitted with fever. One patient had clinical dysentery and group C Salmonella sepsis; the others had mild infection: acute gastroenteritis (n = 2); upper respiratory infection (n = 2); and bronchopneumonia, acute bronchitis, and viral infection (n = 1 each). Two infants were treated with antibiotics. Three infants had neurologic symptoms of ophthalmoplegia with bilateral abduction deficit with or without upbeat nystagmus. All 3 had blood lactic acidosis, and 2 had high cerebrospinal fluid lactate levels. Patient 1, our index case, was hospitalized for upbeat nystagmus and ophthalmoplegia, in addition to daily vomiting episodes since 4 months of age and weight loss of 0.5 kg. Findings on brain computed tomography were normal. Blood lactate levels were high, and TPPE was 37.8%. Brain magnetic resonance imaging (MRI) revealed no abnormalities. Patient 2, who presented at 5 months with lethargy, vomiting, grunting, and abdominal tenderness, was found to have intussusception on abdominal ultrasound and underwent 2 attempts at reduction with air enema several hours apart. However, the lethargy failed to resolve and ophthalmoplegia appeared the next day, leading to suspicions of Wernickes encephalopathy. Laboratory tests showed severe thiamine deficiency (TPPE 31.2%). In patients 1 and 2, treatment led to complete resolution of symptoms. The third infant, a 5-month-old girl, was admitted on October 10, 2003, well before the outbreak was recognized, with vomiting, fever, and ophthalmoplegia. Her condition deteriorated to seizures, apnea, and coma. Brain MRI showed a bilateral symmetrical hyperintense signal in the basal ganglia, mamillary bodies, and periaqueductal gray matter. Suspecting a metabolic disease, vitamins were added to the intravenous solution, including thiamine 250 mg twice a day. Clinical improvement was noted 1 day later. TPPE assay performed after treatment with thiamine was started was still abnormal (17.6%). Her formula was substituted after 4 weeks, after the announcement about the thiamine deficiency. Although the MRI findings improved 5 weeks later, the infant had sequelae of ophthalmoplegia and motor abnormalities and is currently receiving physiotherapy. All 3 patients with neurologic manifestations were fed exclusively with the soy-based formula for 2 to 3.5 months, whereas the others had received solid food supplements. Longer administration of the formula (ie, chronic thiamine deficiency) was associated with failure to thrive. For example, one 12-month-old girl who received the defective formula for 8 months presented with refusal to eat, vomiting, failure to thrive (75th to <5th percentile), hypotonia, weakness, and motor delay. Extensive workup was negative for malabsorption and immunodeficiency. On admission, the patient had Salmonella gastroenteritis and sepsis and was treated with antibiotics. After thiamine deficiency was diagnosed, she received large doses of thiamine (50 mg/day) for 2 weeks. Like the other 5 infants without neurologic involvement, her clinical signs and symptoms disappeared completely within 2 to 3 weeks of treatment, and TPPE levels normalized within 1 to 7 days. There were no side effects. As part of its investigation, the Israel Ministry of Health screened 156 infants who were fed the soy-based formula for thiamine deficiency. However, by that time, most were already being fed alternative formulas and had begun oral thiamine treatment. Abnormal TPPE results (>15%) were noted in 8 infants, 3 male and 5 female, all >1 year old, who were receiving solid food supplements. Although their parents failed to notice any symptoms, irritability, lethargy, vomiting, anorexia, failure to thrive, and developmental delay were documented by the examining physicians. None had signs of neurologic involvement. Treatment consisted of oral thiamine supplements for 2 weeks. Conclusions. Clinician awareness of the possibility of thiamine deficiency even in well-nourished infants is important for early recognition and prevention of irreversible brain damage. Therapy with large doses of thiamine should be initiated at the earliest suspicion of vitamin depletion, even before laboratory evidence is available and before neurologic or cardiologic symptoms appear.

Pediatric Pseudotumor Cerebri Associated With Low Serum Levels of Vitamin A

The aim of this study was to describe the association between pediatric pseudotumor cerebri and low serum vitamin A levels. We retrospectively reviewed the charts of 6 children (5 boys, 1 girl; mean age 8 years) with increased intracranial pressure and low serum vitamin A levels (mean 16.0 ± 8.8 µg/dL). The etiology of the vitamin A deficiency was a restricted diet (2 children), intestinal malabsorption caused by celiac disease (2 children), and undetermined cause (2 children). Only 1 child had ocular signs of xerosis. Poor visual acuity at presentation and lower serum vitamin A levels were associated with a poor visual outcome and development of optic atrophy. In conclusion, pseudotumor cerebri in children can be associated with vitamin A deficiency even when other manifestations of xerophthalmia do not exist. Early recognition of this condition and appropriate therapy can prevent blindness.

The efficacy of asymmetric bilateral medial rectus muscle recession surgery in unilateral, esotropic, type 1 Duane syndrome

BACKGROUND Many patients with esotropic, type 1 Duane syndrome adopt a head turn to gain binocular vision. Numerous surgical procedures have been performed to correct this condition, including asymmetric bilateral medial rectus muscle recession, first proposed by Jampolsky. However, few publications reported on the efficacy of this procedure. METHODS The medical records of patients with unilateral, esotropic Duane syndrome who had asymmetric medial rectus muscle recession for correction of their abnormal head turn were retrospectively reviewed with attention to head turn, ductions, and motor alignment at near and distance fixation. Surgery was considered successful when preoperative head turn was completely eliminated. RESULTS A total of 28 patients (18 females; mean age, 8 years) were included. In 24 patients (86%), the left eye was involved. Medial rectus recession averaged 4.7 mm (range, 3.25-6.0 mm) in the affected eye, with a recession larger by 1.0 mm in the unaffected eye. Average esotropia in the forced primary position improved from 32(Δ) preoperatively to 6(Δ) postoperatively, with a mean 22° improvement in head position (24°-2°). Twenty-four patients (86%) achieved complete resolution of their head turn postoperatively; the other 4 patients experienced partial improvement, with a residual head turn of 10°; a second re-recession of the medial rectus muscle in the affected eye of 1 patient resulted in complete resolution of head turn. CONCLUSIONS Our study showed that asymmetric bilateral medial rectus recession eliminated the head turn in most of our patients with unilateral esotropic Duane syndrome.

Do Intraocular Pressure Measurements Under Anesthesia Reflect the Awake Condition

Background: Anesthesia or sedation is needed when intraocular pressure (IOP) measurement is required in certain circumstances. The effect of different anesthetic regimens on the IOP is still debatable. We aimed to evaluate alterations in the IOP under anesthesia with either propofol or different end-tidal concentrations of sevoflurane, when compared with the awake state. Methods: The IOP was measured in both eyes of 20 adult patients undergoing extraocular ophthalmic surgeries at 5 timepoints: before the induction of general anesthesia (under topical anesthesia), after the induction using propofol target-controlled infusion, and under 3 end-tidal concentrations of sevoflurane (0.5%, 2%, and 5%), either in a decreasing (group A) or an increasing (group B) concentration order. Results: With either propofol or sevoflurane anesthesia, the IOP did not differ significantly from the measurement performed during the awake state (no anesthesia), regardless of the concentration of sevoflurane used (in the range of 0.5% to 5%) or the order of sevoflurane administration (from low to high concentration or vice versa). Conclusions: These data suggest that propofol and sevoflurane are valid anesthetic agents for the evaluation of IOP in adults when anesthesia is needed.

Color Doppler imaging of eyes with persistent fetal vasculature

BackgroundEyes with persistent fetal vasculature (PFV) may be mistaken for retinoblastoma and provide a diagnostic challenge.ObjectiveThis study aimed to evaluate the role of color Doppler imaging (CDI) in children with persistent fetal vasculature.Materials and methodsEyes with a diagnosis of PFV were evaluated by CDI.ResultsTwenty eyes of 17 children were included. All had a confirmed diagnosis of PFV based on one or more of the following: clinical findings on funduscopy, characteristic findings on imaging modalities (ophthalmic gray-scale US, CT and/or MRI), typical findings observed intraoperatively, and histopathological analysis (after enucleation in one case). Blood flow within the PFV was demonstrated in 19 eyes in this series.ConclusionCDI is a noninvasive diagnostic tool that may add useful information on the presence of blood flow within the PFV and may substantiate the diagnosis of PFV in cases of uncertainty.

Comparison of Ishihara Booklet with Color Vision Smartphone Applications.

Purpose To compare the standard Ishihara booklet with color-vision-testing smartphone applications. Methods A prospective observational diagnostic study on 42 normal trichromats and 38 color-deficient subjects. Patients were presented with three color vision tests in random order: an Ishihara test booklet and two color-vision-testing smartphone applications: Eye2Phone and the Color Vision Test application (CVT app). Sensitivity and specificity of the electronic tests was compared with Ishihara results, and in each one of these applications every plate was individually analyzed for success/failure rate. Results Average age was 42.7 ± 12.9 years. There were 57 males (71.2%). Sensitivity and specificity of each test was 100% (38/38) and 95.2% (40/42) for the Eye2Phone, and 100% (38/38) and 54.8% (23/42) for the CVT app. There was no significant difference between the Ishihara booklet and the Eye2Phone (p = 0.500), with a high kappa measure of agreement (0.950, p < 0.001). The CVT app was significantly different than both other tests (p < 0.001) with a low kappa measure of agreement (0.535 with the Ishihara and 0.575 with the Eye2Phone). Of the 21 tested plates, color-deficient subjects failed 11.8 ± 3.1 plates in the Ishihara booklet and 14.1 ± 2.1 plates in the Eye2Phone (p < 0.001). Significant plate-specific differences for the color-deficient group were found in plate numbers 3, 6, 7, 8, 9, 15, and 16. Both tests were poorly able to give an indication of the specific dichromatism type. The Ishihara booklet was rated more comfortable and clearer than the Eye2Phone in color-deficient subjects. The CVT app was rated lowest for comfort and clarity in both groups. Conclusions Smartphone applications testing for color vision deficiency are readily available; however, users of these apps should be aware that some may have different sensitivity for detection of color vision deficiency compared to Ishihara booklet, limiting their usefulness for clinical use. Therefore, further validation of these applications is required.

Surgical Outcome of Strabismus Surgery in Patients With Unilateral Vision Loss and Horizontal Strabismus

PURPOSE To report on the surgical outcome of horizontal strabismus surgery in patients diagnosed as having unilateral vision loss. METHODS Medical records of all patients with unilateral vision loss who underwent surgical repair of horizontal strabismus between 2008 and 2013 at three medical centers were reviewed. Data collected included age at time of surgery, type of strabismus, preoperative and postoperative deviation, procedure performed, and length of follow-up. Surgical success was defined as final alignment of 10 prism diopters (PD) or less unless more than one surgery was required to realign the eyes. RESULTS Twenty-one patients (9 children) were reviewed. Mean age at time of surgery was 28.3 years (range: 3 to 64 years) and mean follow-up was 20 months (range: 6 months to 5 years). Mean preoperative logMAR visual acuity in the deviating eyes (14 right eyes) was 1.4 ± 0.7 (range: 1.0 to 2.8) and mean deviation was 33 PD (range: 15 to 90 PD). All procedures were performed only on the deviating eye (13 recessions and 8 recession-resection procedures). Mean postoperative deviation was 6.4 PD (range: 0 to 25 PD) and 81% of patients had a manifest ocular deviation of 10 PD or less. Surgical success was comparable in children versus adults (P = .603), in patients with esotropia versus exotropia (P = 1.000), in patients with preoperative deviations larger than 30 PD compared to patients with smaller deviations (P = .521), and in patients in whom one muscle was operated on compared to all other patients (P = .617). CONCLUSIONS Strabismus surgery in patients with unilateral vision loss is often successful in correcting ocular misalignment.

Refractive Changes Induced by Strabismus Corrective Surgery in Adults

Purpose. To investigate refractive changes after strabismus correction procedures among adults. Methods. Retrospective chart review of adult patients who had horizontal recti muscles surgery with preoperative and postoperative cycloplegic refraction measurements. The preoperative refraction was mathematically subtracted from the postoperative refraction, and the induced refractive changes were statistically analyzed. Vector analysis was used to examine the magnitude of the toric change. The proportion of clinically significant refractive change was evaluated as well. Results. Thirty-one eyes from 22 subjects met the criteria and were included in the final analysis. A significant postoperative refractive change of the spherical equivalent towards myopia and a change of the astigmatism in the with-the-rule direction were observed. In a subset of 9 cases a third cycloplegic refraction measurement demonstrated stable refraction compared to the 1-month postoperative measurement. In 10 cases of single eye surgery, significant refractive changes were observed only in the operated side when compared to the sound eye. The induced surgical refractive change was of clinical significance (≥0.5 D) in 11 eyes of 9 patients (40.9% of patients). Conclusions. Refractive changes are a significant side effect of horizontal strabismus corrective surgery among adults. Therefore, patients should be informed about it prior to surgery and should be rerefracted in the postoperative period.

Extraocular muscle damage from dental implant penetration to the orbit

Purpose To demonstrate an unusual case of orbital trauma due to dental surgery complication. Observations An elderly patient who underwent dental implantation to the zygomatic bone was hospitalized in the ophthalmology department with impaired abduction of her right eye, also evident on ocular examination. Head computed tomography demonstrated damage to the lateral rectus and to the inferior oblique muscles. Clinical assessment determined these muscles could not be repaired and reattached. The extent of irreversible damage in the patient was permanent limitation in movement of her affected eye with subsequent strabismus. Conclusions and importance Accurate pre-operative planning of dental zygomatic implant insertion, as well as selecting the size and direction of the implant, are imperative. Moreover, performing surgery in multidisciplinary centers with oculofacial plastic surgeons in such cases, may reduce risk of this complication, make it a safer procedure, and allow immediate treatment when required.

Macular Thickness Following Strabismus Surgery as Determined by Optical Coherence Tomography

PURPOSE To investigate macular changes following strabismus surgery by using optical coherence tomography (OCT). METHODS The authors prospectively evaluated 60 eyes of 30 patients undergoing unilateral extraocular muscle surgery. OCT measurements employing the fast macular thickness mapping protocol were performed 1 day prior to surgery and 1 day postoperatively. Postoperative macular changes in the study eye that was operated on (n = 30) were compared with the fellow control eye (n = 30, controls). RESULTS There was an increase in mean ± standard deviation central foveal thickness (CFT) in the operated eyes, from 201.63 ± 18.36 µm at baseline to 206.03 ± 22.73 µm postoperatively (P = .024). Preoperative and postoperative perifoveal outer temporal quadrant thicknesses were 220.10 ± 16.23 and 225.80 ± 14.78 µm, respectively (P = .009). There were no differences between preoperative and postoperative retinal thickness measurements for all measured areas in the control eyes. Eyes that underwent surgery involving the rectus muscles showed a trend toward a greater CFT increase compared with eyes that had oblique muscle surgery (P = .070). CONCLUSIONS The authors found subclinical increases in the foveal and perifoveal macular thicknesses following extraocular muscle surgery. These findings could be attributed to change in the mechanical forces caused by the new position of the extraocular muscles and transmitted via the sclera or, alternatively, to postoperative inflammation and alterations in the blood-retinal barrier. The clinical implications of these findings remain to be clarified.