BILATERAL PARACENTRAL ACUTE MIDDLE MACULOPATHY AFTER CARDIOPULMONARY BYPASS.

PURPOSE: To report the first two observations of bilateral paracentral acute middle maculopathy in the early postoperative period after cardiopulmonary bypass procedures. METHODS: Comprehensive ophthalmic examinations were performed, including best-corrected visual acuity, Humphrey visual field testing, dilated fundus examination, and optical coherence tomography. RESULTS: Two patients complained of unilateral vision loss after cardiac surgery involving cardiopulmonary bypass. Unilateral optic disc edema consistent with ischemic optic neuropathy was observed in the symptomatic eye of each patient, whereas scattered cotton-wool spots were identified bilaterally. In addition, optical coherence tomography imaging revealed bilateral paracentral acute middle maculopathy, correlating with visual field defects detected on automated perimetry in the asymptomatic eyes. CONCLUSION: Although symptomatic postoperative vision loss is a rare complication of cardiac surgery, intraoperative retinal microvascular nonperfusion as a consequence of extracorporeal circulation of blood may be a more common and under-recognized occurrence.

Decreased ACKR3 (CXCR7) function causes oculomotor synkinesis in mice and humans.

Oculomotor synkinesis is the involuntary movement of the eyes or eyelids with a voluntary attempt at a different movement. The chemokine receptor CXCR4 and its ligand CXCL12 regulate oculomotor nerve development; mice with loss of either molecule have oculomotor synkinesis. In a consanguineous family with congenital ptosis and elevation of the ptotic eyelid with ipsilateral abduction, we identified a co-segregating homozygous missense variant (c.772G>A) in ACKR3, which encodes an atypical chemokine receptor that binds CXCL12 and functions as a scavenger receptor, regulating levels of CXCL12 available for CXCR4 signaling. The mutant protein (p.V258M) is expressed and traffics to the cell surface but has a lower binding affinity for CXCL12. Mice with loss of Ackr3 have variable phenotypes that include misrouting of the oculomotor and abducens nerves. All embryos show oculomotor nerve misrouting, ranging from complete misprojection in the midbrain, to aberrant peripheral branching, to a thin nerve, which aberrantly innervates the lateral rectus (as seen in Duane syndrome). The abducens nerve phenotype ranges from complete absence, to aberrant projections within the orbit, to a normal trajectory. Loss of ACKR3 in the midbrain leads to downregulation of CXCR4 protein, consistent with reports that excess CXCL12 causes ligand-induced degradation of CXCR4. Correspondingly, excess CXCL12 applied to ex vivo oculomotor slices causes axon misrouting, similar to inhibition of CXCR4. Thus, ACKR3, through its regulation of CXCL12 levels, is an important regulator of axon guidance in the oculomotor system; complete loss causes oculomotor synkinesis in mice, while reduced function causes oculomotor synkinesis in humans.

Retinal thinning in amyotrophic lateral sclerosis patients without ophthalmic disease.

IMPORTANCE: Amyotrophic lateral sclerosis (ALS) is a fatal, rapidly progressive neurodegenerative disease that primarily affects motor neurons. Recently, three causative genes have been implicated in both ALS and glaucoma. However, it is still uncertain whether patients with ALS have neurodegeneration in their retinas. If so, retinal thickness measurements might be a useful biomarker for ALS progression. Previous work in this area has been inconclusive, as it has not taken into account the effect of ophthalmic diseases on retinal thinning. OBJECTIVE: To determine whether there are differences in retinal neurons in ALS patients utilizing spectral-domain optical coherence tomography (SD-OCT). We tested the hypothesis that ALS patients exhibit retinal neurodegeneration that is not associated with ophthalmic diseases. DESIGN, SETTINGS AND PARTICIPANTS: Observational, comparative, cross-sectional study performed on patients recruited from the Duke University Medical Center ALS clinic. Patients underwent a comprehensive ophthalmologic examination to rule out ocular pathology. 21 patients met inclusion criteria. Two eyes with ocular pathology were excluded, leading to a total of 40 eyes of 21 patients included in the study. Retinal neurodegeneration was assessed by retinal nerve fiber layer (RNFL) thickness measurement using SD-OCT (Spectralis; Heidelberg Engineering). MAIN OUTCOMES AND MEASURES: ALS disease severity, determined through the ALS Functional Rating Scale (ALSFRS-R); mean and six sector RNFL thickness values compared to age-adjusted values in the normative database provided by Heidelberg Engineering; RNFL thickness correlation with ALSFRS-R, ALSFRS-R progression rate, forced vital capacity (FVC), and visual acuity. RESULTS: ALSFRS-R mean score was 30+/-10. Mean RNFL thickness in ALS patients was 88.95 +/- 10.8 microns, significantly thinner than values in the normative database (95.81 +/- 0.8). These RNFL thickness values did not demonstrate correlation to ALSFRS-R score, ALSFRS-R progression rate, FVC, intraocular pressure, or visual acuity. CONCLUSIONS: Using SD-OCT, our study shows that ALS patients without ocular pathology exhibit thinned retinal layers. Future studies are warranted to clarify the clinical relationship between retinal thinning and motor neuron loss in ALS.

Diagnosis and management of opacified silicone intraocular lenses in patients with asteroid hyalosis.

UNLABELLED: We analyzed 3 calcified silicone IOLs from 2 patients with a history of asteroid hyalosis. In both cases, posterior capsule opacification had been diagnosed and a laser capsulotomy performed before referral. Subsequently, both IOLs were exchanged with hydrophobic acrylic IOLs that were placed in the sulcus. The IOL exchange was challenging due to the open capsule. Light microscopy demonstrated that the white deposits on the explanted IOLs formed an almost confluent crust in some areas, interspersed with clear areas on the posterior optic surfaces. The findings in our cases and in other reported cases may affect the choice of IOL in the presence of asteroid hyalosis. Also, ophthalmologists may consider deferring laser posterior capsulotomy treatment in a calcified silicone IOL to facilitate an IOL exchange procedure. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Update on the surgical management of idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH) is a disorder of elevated intracranial pressure due to an unknown cause. In most cases, IIH can be managed with medical therapy and weight reduction. Surgical treatment of IIH is reserved for patients who cannot tolerate medical therapy, are nonadherent to medical therapy, develop progressive symptoms despite maximal medical therapy, or present with fulminant visual loss. To date, there has been no randomized controlled trial to evaluate the surgical treatment of IIH, and our current knowledge of the efficacy and complications of these procedures is based on retrospective and observational studies. This review discusses the indications for surgical intervention in IIH and provides an overview of the recently published data on the efficacy and complications of these interventions. A surgical management algorithm is also presented to guide the clinician when evaluating a patient with IIH.

Segmentation and quantification of pulmonary artery for noninvasive CT assessment of sickle cell secondary pulmonary hypertension.

PURPOSE: Pulmonary arterial hypertension (PAH) is a progressive vascular disease that results in high mortality and morbidity in sickle cell disease (SCD) patients. PAH diagnosis is invasive via right heart catheterization, but manual measurements of the main pulmonary artery (PA) diameters from computed tomography (CT) have shown promise as noninvasive surrogate marker of PAH. The authors propose a semiautomated computer-assisted diagnostic (CAD) tool to quantify the main PA size from pulmonary CT angiography (CTA). METHODS: A follow-up retrospective study investigated the potential of CT and image analysis to quantify the presence of PAH secondary to SCD based on PA size. The authors segmented the main pulmonary arteries using a combination of fast marching level sets and geodesic active contours from smoothed pulmonary CTA images of 20 SCD patients with proven PAH by right heart catheterization and 20 matched negative controls. From the PA segmentation, a Euclidean distance map was calculated and an algorithm based on fast marching methods was used to compute subvoxel precise centerlines of the PA trunk (PT) and main left/right PA (PM). Maximum distentions of PT and PM were automatically quantified using the centerline and validated with manual measurements from two observers. RESULTS: The pulmonary trunk and main were significantly larger (p < 0.001) in PAH/SCD patients (33.73 +/- 3.92 mm for PT and 25.17 +/- 2.90 for PM) than controls (27.03 +/- 2.94 mm for PT and 20.62 +/- 3.06 for PM). The discrepancy was qualitatively improved when vessels' diameters were normalized by body surface area (p < 0.001). The validation of the method showed high correlation (mean R=0.9 for PT and R = 0.91 for PM) and Bland-Altman agreement (0.4 +/- 3.6 mm for PT and 0.5 +/- 2.9 mm for PM) between CAD and manual measurements. Quantification errors were comparable to intraobserver and interobserver variability. CAD measurements between two different users were robust and reproducible with correlations of R = 0.99 for both PT and PM and Bland-Altman agreements of -0.13 +/- 1.33 mm for PT and -0.08 +/- 0.84 mm for PM. CONCLUSION: Results suggest that the semiautomated quantification of pulmonary artery has sufficient accuracy and reproducibility for clinical use. CT with image processing and extraction of PA biomarkers show great potential as a surrogate indicator for diagnosis or quantification of PAH, and could be an important tool for drug discovery and noninvasive clinical surveillance.

The association between early outcome, health-related quality of life, and survival following elective open-heart surgery.

We investigated the impact of perioperative complications on patients' health-related quality of life (HRQL) and intermediate-term survival after cardiac surgery. Improved results for cardiac surgery are well demonstrated in low rates of operative mortality and morbidity. However, the association between perioperative morbid events, HRQL at 1 year, and survival is unclear. We performed a prospective study among 836 elective cardiac surgery patients to assess the impact of perioperative outcomes on survival and HRQL at 1 year. Health-related quality of life was generated using the 20-item short-form questionnaire. Kaplan-Meier and life-table estimates were used to examine the relationship of HRQL at 1-year and intermediate-term survival. All HRQL domains were statistically improved at 1 year, with the highest gains in general health perception (+19.4%) and the least gains in social (+5.1%) and mental (+5.1%) domains. Patients experiencing 1 or more perioperative complication or increased length of stay reported similar HRQL scores as patients with no complications. Patients with negative changes in social (94.5% vs 99.2%, P < .001) and general health perception (99.4% vs 95.5%, P < .001) domains showed a reduced survival compared with patients with positive HRQL gains at 2 to 5 years after surgery. Perioperative complications had minimal or no effect on HRQL at 1 year after cardiac surgery.

CT and image processing non-invasive indicators of sickle cell secondary pulmonary hypertension.

This retrospective study investigates the potential of image analysis to quantify for the presence and extent of pulmonary hypertension secondary to sickle cell disease (SCD). A combination of fast marching and geodesic active contours level sets were employed to segment the pulmonary artery from smoothed CT-Angiography images from 16 SCD patients and 16 matching controls. An algorithm based on fast marching methods was used to compute the centerline of the segmented arteries to measure automatically the diameters of the pulmonary trunk and first branches of the pulmonary arteries. Results show that the pulmonary trunk and arterial branches are significantly larger in diameter in SCD patients as compared to controls (p-values of 0.002 for trunk and 0.0003 for branches). For validation, the results were compared with manually measured values and did not demonstrate significant difference (mean p-values 0.71). CT with image processing shows great potential as a surrogate indicator of pulmonary hemodynamics or response to therapy, which could be an important tool for drug discovery and noninvasive clinical surveillance.