Ultra-widefield fundus autofluorescence imaging in patients with autosomal recessive retinitis pigmentosa reveals a genotype-phenotype correlation.

PURPOSE: To analyze the genotype-phenotype correlation in patients with retinitis pigmentosa (RP) caused by mutations in the FAM161A, DHDDS, or MAK genes using ultra-widefield fundus autofluorescence (UWF-FAF) imaging. METHODS: Retrospective case series of patients with autosomal recessive RP (ARRP) with confirmed causative genetic mutations and available UWF-FAF imaging data. The UWF-FAF data were graded in a blinded fashion using the following criteria: the pattern of macular abnormalities on FAF, the presence or absence of horizontal linear hyperautofluorescence, the extent of decreased autofluorescence (DAF), the shape of DAF, and the presence of hyperautofluorescence at the optic disk. RESULTS: A total of 43 patients (mean age of 47 ± 16 years, ranging from 17 to 79 years) with ARRP (86 eyes) were included in our analysis. Genotyping data revealed biallelic mutations in the FAM161A, DHDDS, and MAK genes in 20, 12, and 11 patients, respectively. We found significant differences between the three groups with respect to the pattern of macular abnormalities on FAF (p = 0.001), DAF configuration (p = 0.007), and extent of DAF (p = 0.037). The largest difference between groups was found for macular abnormalities on FAF, with DHDDS patients differing significantly from the MAK and FAM161A groups (p = 0.001). Specifically, DHDDS patients had a more abnormal macular FAF pattern and more widespread decrease in peripheral autofluorescence. No other parameters differed significantly between the three groups. CONCLUSIONS: Patients with ARRP can present with specific UWF-FAF patterns based on the underlying causative gene. Future studies are warranted in order to expand this analysis to include additional genes, mutations, and patients as well as assessment of disease progression by following patients over longer periods of time.

Characterizing the Response to Cerebrospinal Fluid Drainage in Patients with an External Ventricular Drain: The Pressure Equalization Ratio.

BACKGROUND: An external ventricular drain (EVD) is the gold standard for measurement of intracranial pressure (ICP) and allows for drainage of cerebrospinal fluid (CSF). Different causes of elevated ICP, such as CSF outflow obstruction or cerebral swelling, respond differently to CSF drainage. This is a widely recognized but seldom quantified distinction. We sought to define an index to characterize the response to CSF drainage in neurocritical care patients. METHODS: We studied consecutive patients admitted to the neurointensive care unit who had an EVD. The EVD was closed for 30 min prior to assessment. We documented pre-drainage ICP, opened EVD to drainage allowing CSF to drain until it ceased, and recorded post-drainage ICP at EVD closure. We calculated the pressure equalization (PE) ratio as the difference between pre-drainage ICP and post-drainage ICP divided by the difference between pre-drainage ICP and EVD height. RESULTS: We studied 60 patients (36 traumatic brain injury [TBI], 24 non-TBI). As expected, TBI patients had more signs of cerebral swelling on CT and smaller ventricles. Although TBI patients had significantly higher pre-drainage ICP (26 ± 10 mm Hg) than non-TBI patients (19 ± 5 mm Hg, p < 0.001) they drained less CSF (7 cc vs. 4 cc, p < 0.01). PE ratio was substantially higher in non-TBI than in TBI patients (0.86 ± 0.36 vs. 0.43 ± 0.31, p < 0.0001), indicating that non-TBI patients were better able to equalize pressure with EVD height than TBI patients. CONCLUSIONS: PE ratio reflects the ability to equalize pressure with the preset height of the EVD and differs substantially between TBI and non-TBI patients. A high PE ratio likely indicates CSF outflow obstruction effectively treated by CSF diversion, while a lower PE ratio occurs when cerebral swelling predominates. Further studies could assess whether the PE ratio would be useful as a surrogate marker for cerebral edema or the state of intracranial compliance.

Advanced Optical Analysis of Divergence Between the Foci of the Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) and Aiming Beam Lasers.

Purpose: To evaluate the divergence between the neodymium-doped yttrium aluminum garnet (Nd:YAG) surgical laser and the aiming diode laser beams foci. Design: Optical analysis and measurements were performed using a Volk Goldmann 3-mirror lens with a Nidek YC-1800 Nd:YAG laser apparatus. Subjects: None. Methods: We used the Zemax OpticStudio program for the model of Nd:YAG treatment in a human eye. Additionally, theoretical calculations were performed. Main Outcome Measures: The divergence between the Nd:YAG laser focus and the intersection of the 2 aiming beams inside the eye. Results: Focal points of the 2 laser beams converge 8 mm behind the cornea. Posterior to this point, the intersection of the diode laser aiming beams lies in front of the focal point of the Nd:YAG treatment laser, with distance between the 2 foci progressively increasing up to 305 microns at 24 mm behind the cornea. Conclusions: We report the degree of divergence between the 2 lasers' focal points due to the difference in refraction between the corresponding wavelengths. These results have high practical relevance, as they provide a starting point for increasing the accuracy of Nd:YAG laser treatment, particularly when applied to the posterior segment, thereby minimizing the risk of complications. Current Nd:YAG laser devices have the built-in ability to modify the focal point of the aiming beam along the z-axis, thus providing possibility for an immediate application of our findings in clinical practice. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

[The effect of platelet transfusion on traumatic intracranial hemorrhage among patients treated with aspirin].

BACKGROUND: Head trauma represents a serious medical and socio-economical problem owing to its related morbidity and mortality. One of its serious complications is traumatic intracranial hemorrhage (TICH). There is evidence that TICH has a tendency to expand, especially during the first hours following injury. Aspirin has a central role in preventing thromboembolic complications in atherosclerotic conditions. This effect is mediated through the inhibition of platelet activity. There is a theoretical concern that treatment prior to the head injury with aspirin may expand the size of TICH. The purpose of the current study was to evaluate the effect of platelet transfusion on the extent of TICH expansion among patients treated with aspirin. METHODS: This retrospective study includes patients admitted to the Tel-Aviv Medical Center and the Tel-Hashomer Medical Center between 1/12/2004 and 31/10/2008. Patients were included if they underwent closed head injury, were treated regularly with aspirin prior to the injury, and had radiological evidence of an intraparenchymal hemorrhage or contusion (IPHC) or an acute subdural hematoma (ASDH]. The interval between the injury and the first computed tomography [CT] scan was not longer than 12 hours, and the interval between the first CT scan and the control CT scan was not longer than 24 hours. The effect of platelet transfusion administered between these two CT scans on the radiological and clinical outcomes was evaluated by a comparison between a group of patients treated with platelet transfusion (group A) and a group of patients who weren't treated with it (group B). RESULTS: A total of 44 patients were included in the study: 14 patients had IPHC, 40 had ASDH and 10 had both IPHC and ASDH. In the IPHC group the frequency of hemorrhagic expansion and the extent of expansion were greater in group A than in group B. Possibly, an earlier first CT, longer duration between both CT scans and a larger hemorrhage volume on CT1 in group A may explain these differences. In the ASDH group the frequency of hemorrhagic expansion was lower in group A than in group B, but without statistical significance. There was no significant difference in the extent of hemorrhagic expansion between the two treatment groups. CONCLUSIONS: From this study it appears that platelet transfusion within 36 hours post injury for patients with TICH who were treated with aspirin prior to the head injury does not reduce the rate or extent of hemorrhagic expansion. However, owing to the limitations of the present study, this conclusion should be considered with caution. We recommend evaluating this issue in a prospective, randomized, multi-center study.

Childhood visual impairment and blindness: 5-year data from a tertiary low vision center in Israel.

BACKGROUND: To assess the main causes leading to childhood visual impairment/blindness in a center for low vision in Israel and to analyze the literature on pediatric blinding diseases in developed countries. METHODS: Retrospective study based on observational case series. Data were obtained from medical records of visually impaired children, seen at a national referral low vision center. Children were divided into two groups: moderate visual impairment (6/18 to 6/60) and severe visual impairment (SVI)/blindness (<6/60). Inherited eye diseases (IED) were grouped together for analysis. Data from the Israeli blind registry from the same period of time were analyzed for comparison. A review of literature on childhood blindness in developed countries since 2000 was conducted. RESULTS: A total of 1393 children aged 0-18 years were included in the study. Moderate visual impairment was seen in 1025 (73.6%) and SVI/blindness in 368 (26.4%) of the studied children. Among blind children, IED accounted for at least 51% of all diagnoses, including mainly albinism and retinal dystrophies. IED prevalence was equally high in both main ethnic groups (Jewish and Arab Muslims). Non-IED (22.6%) included mainly patients with cerebral visual impairment and retinopathy of prematurity. CONCLUSIONS: The leading cause of childhood visual impairment and blindness in our patient cohort was IED. Analyses of the literature from the last two decades show that IED are a major cause for SVI/childhood blindness in other developed countries as well. Updated patterns of global childhood blindness may suggest a need for new approach for screening programs and modern tactics for prevention.

[The dilemma regarding treatment of pulmonary embolism among elderly patients].

Pulmonary embolism is a medical condition associated with significant morbidity and mortality. However, there are serious side effects to the anticoagulation therapy. We report on a 97-year-old woman who was admitted to the internal medicine department due to dyspnea and pleuritic chest pain. In the differential diagnosis we considered pulmonary embolism. In this article we present the diagnostic and therapeutic steps according to the guidelines, and compare them to a hypothetical situation of a younger woman who is presented with the same clinical findings. We discuss the risks that are attributed to pulmonary embolism on the one hand, and to the anticoagulation therapy on the other hand, with respect to elderly patients more than 80 and 90 years old versus younger patients.

Acquired unilateral visual deterioration: More to ischemia than meets the eye.

A 56-year-old woman presented with visual loss in the right eye with best-corrected visual acuity of 20/40. Funduscopic examination revealed neovascularization of the disk with peripapillary preretinal hemorrhages and leakage on fluorescein angiography. Cerebral arteriography demonstrated stenosis of the major cerebral vessels with classic collaterals configuring as "puff of smoke." A diagnosis of moyamoya-related ocular ischemic syndrome manifesting with optic disk neovascularization was made.