Saitakis G, Chwalisz BK.
The neurology of IGG4-related disease. J Neurol Sci 2021;424:117420.
AbstractPURPOSE OF REVIEW: IgG4-related disease (IgG4-RD) is emerging as a fibro-inflammatory entity affecting multiple organs, including manifold neurologic manifestations. This review discusses general characteristics of IgG4-RD neurologic disease including epidemiology, histology, clinical picture and treatment approaches. RECENT FINDINGS: IgG4-RD is increasingly recognized as an important underlying pathophysiology in multiple disorders of neurologic interest, including orbital inflammation, infundibulo-hypophysitis, hypertrophic pachymeningitis, and even in rare cases CNS parenchymal disease and cranial vascular involvement. These were previously considered idiopathic and unrelated to any systemic disease but now known to share a common histopathology. New knowledge regarding the pathogenesis, clinical features and epidemiology of IgG4 is emerging, and new neurological manifestations continue to be described. Diagnostic progress includes CT-PET imaging, the use of flow cytometry for plasmablast quantification, and the use of reverse passive latex agglutination aiming to overcome the prozone phenomenon. Histopathologic confirmation of IgG4-RD remains the gold standard method of diagnosis but new diagnostic criteria for systemic and organ-specific disease are being proposed. Though glucorticoids remain the mainstay of therapy, relapses and incomplete recovery are frequent. Rituximab is a promising treatment in IgG4-RD that is severe, refractory or glucocorticoid dependent. Initiation of immunosuppression at an early stage of disease should be considered in order to avoid development of refractory fibrosis. SUMMARY: The current review emphasizes the neurologic manifestations of IgG4-RD.
Scelfo C, Mantagos IS.
Neurotrophic Keratopathy in Pediatric Patients. Semin Ophthalmol 2021;36(4):289-295.
AbstractPurpose: This review provides an overview of the causes and treatment of neurotrophic keratopathy in the pediatric population.Methods: A thorough review of the current literature discussing neurotrophic keratopathy was conducted then summarized.Results:Fourty-nine papers were reviewed. Congenital and acquired causes of neurotrophic keratopathy exist in the pediatric population. Both medical and surgical approaches to treatment have been trialed, albeit to a limited extent, in pediatric patients. Conservative treatment includes topical lubrication and antibiotics to prevent concurrent infectious ulcer formation. Various neurotrophic factors have been trialed in the form of serum drops to restore corneal sensation when conservative measures fail. Surgically, different corneal neurotization techniques have been developed whereby a donor nerve is routed to the anesthetized cornea to restore innervation and sensation. Conclusions: Advances in the treatment of neurotrophic keratopathy have made corneal reinnervation and restoration of vision more easily attainable in pediatric patients.
Shoshany TN, Chinn RN, Staffa SJ, Bishop K, Michalak S, Hunter DG.
Identifying Characteristics Predictive of Lost-to-follow-up (LTFU) Status in Amblyopia. Am J Ophthalmol 2021;
AbstractPURPOSE: To identify demographic and disease-related characteristics predictive of LTFU status in amblyopia treatment and create a risk model for predicting LTFU status. DESIGN: Retrospective cohort study METHODS: Setting: Single center, ophthalmology department at Boston Children's Hospital (BCH). PATIENTS: 2037 patients treated for amblyopia at BCH between 2010-2014. OBSERVATION PROCEDURE: LTFU was defined as patients who did not return after initial visit, excluding those who came for second opinion. Multiple variables were tested for association with LTFU status. OUTCOME MEASURE: Odds ratio of LTFU risk associated with each variable. Multivariate logistic regression was used to create a risk score for predicting LTFU status. RESULTS: A large proportion of patients (23%) were LTFU after first visit. Older age, non-white race, lack of insurance, previous glasses or atropine treatment, and longer requested follow-up intervals were independent predictors of LTFU status. A multivariable risk score was created to predict probability of LTFU (AUC 0.68). CONCLUSIONS: Our comprehensive amblyopia database allows us to predict which patients are more likely to be LTFU after baseline visit, and develop strategies to mitigate these effects. These findings may help with practice efficiency and improve patient outcomes in the future by transitioning these analyses to an electronic medical record that could be programmed to provide continually updated decision support for individual patients based on large datasets.
Silva RNE, Chiou CA, Wang M, Devlin J, Li D, Lovelace S, Wang H, Greenstein SH, Brauner SC, Shen LQ.
Quantification of the Peripapillary Microvasculature in Eyes with Glaucomatous Paracentral Visual Field Loss. Ophthalmol Glaucoma 2021;4(3):286-294.
AbstractPURPOSE: To quantify abnormalities in the peripapillary microvasculature in eyes with primary open-angle glaucoma (POAG) and paracentral visual field (VF) loss. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Thirty-three POAG patients, including 15 with paracentral VF loss and 18 with peripheral VF loss, and 31 control participants underwent swept-source OCT angiography (OCTA) of the peripapillary region. METHODS: The POAG groups were matched by VF mean deviation (MD). The peripapillary microvasculature from the internal limiting membrane to the retinal nerve fiber layer (RNFL) interface was quantified within a 0.70-mm annulus around Bruch's membrane opening after removal of large vessels. Both vessel density (VD) and the integrated OCTA by ratio analysis signal (IOS) suggestive of flow were measured. Regional VD and IOS were measured from the affected hemisphere corresponding to the VF hemifield of more severe loss, which was used to calculate the paracentral total deviation (PaTD), or total deviation within the central 10°. One eye per participant was included. MAIN OUTCOME MEASURES: Difference in peripapillary OCTA measurements between paracentral and peripheral VF loss groups and correlation of peripapillary VD and IOS with PaTD. RESULTS: The POAG groups had matched VF MD (-3.1 ± 2.5 dB paracentral vs. -2.3 ± 2.0 dB peripheral; P = 0.31), did not differ in average RNFL thickness (71.1 ± 14.7 μm vs. 78.1 ± 15.0 μm; P = 0.55), but differed in age (59.2 ± 9.6 years paracentral vs. 67.4 ± 6.6 years peripheral; P = 0.02). Compared with control participants, both paracentral and peripheral VF loss groups showed reduced VD (P < 0.001 and P = 0.009, respectively) and IOS (P < 0.001 and P = 0.01, respectively) in the affected hemisphere. Compared with POAG eyes with peripheral VF loss, the paracentral group showed reduced peripapillary VD (38.0 ± 2.0%, 35.0 ± 2.2%, respectively; P = 0.001) and IOS (44.3 ± 3.1%, 40.4 ± 4.0%, respectively; P = 0.02) in the affected hemisphere. Among all POAG eyes, peripapillary VD and IOS of the affected hemisphere correlated significantly with functional measurement of paracentral loss (PaTD, r = 0.40, P = 0.02; r = 0.45, P = 0.008; respectively). These correlations remained significant after adjusting for age (r = 0.41, P = 0.02; r = 0.47, P = 0.01; respectively). CONCLUSIONS: Regional peripapillary microvasculature showed decreased VD and flow in POAG with paracentral loss, supporting its importance in this glaucoma subtype.
Simpson FC, McTiernan CD, Islam MM, Buznyk O, Lewis PN, Meek KM, Haagdorens M, Audiger C, Lesage S, Gueriot F-X, Brunette I, Robert M-C, Olsen D, Koivusalo L, Liszka A, Fagerholm P, Gonzalez-Andrades M, Griffith M.
Collagen analogs with phosphorylcholine are inflammation-suppressing scaffolds for corneal regeneration from alkali burns in mini-pigs. Commun Biol 2021;4(1):608.
AbstractThe long-term survival of biomaterial implants is often hampered by surgery-induced inflammation that can lead to graft failure. Considering that most corneas receiving grafts are either pathological or inflamed before implantation, the risk of rejection is heightened. Here, we show that bioengineered, fully synthetic, and robust corneal implants can be manufactured from a collagen analog (collagen-like peptide-polyethylene glycol hybrid, CLP-PEG) and inflammation-suppressing polymeric 2-methacryloyloxyethyl phosphorylcholine (MPC) when stabilized with the triazine-based crosslinker 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride. The resulting CLP-PEG-MPC implants led to reduced corneal swelling, haze, and neovascularization in comparison to CLP-PEG only implants when grafted into a mini-pig cornea alkali burn model of inflammation over 12 months. Implants incorporating MPC allowed for faster nerve regeneration and recovery of corneal sensation. CLP-PEG-MPC implants appear to be at a more advanced stage of regeneration than the CLP-PEG only implants, as evidenced by the presence of higher amounts of cornea-specific type V collagen, and a corresponding decrease in the presence of extracellular vesicles and exosomes in the corneal stroma, in keeping with the amounts present in healthy, unoperated corneas.
Styliadis C, Leung R, Özcan S, Moulton EA, Pang E, Taylor MJ, Papadelis C.
Atypical spatiotemporal activation of cerebellar lobules during emotional face processing in adolescents with autism. Hum Brain Mapp 2021;42(7):2099-2114.
AbstractAutism spectrum disorder (ASD) is characterized by social deficits and atypical facial processing of emotional expressions. The underlying neuropathology of these abnormalities is still unclear. Recent studies implicate cerebellum in emotional processing; other studies show cerebellar abnormalities in ASD. Here, we elucidate the spatiotemporal activation of cerebellar lobules in ASD during emotional processing of happy and angry faces in adolescents with ASD and typically developing (TD) controls. Using magnetoencephalography, we calculated dynamic statistical parametric maps across a period of 500 ms after emotional stimuli onset and determined differences between group activity to happy and angry emotions. Following happy face presentation, adolescents with ASD exhibited only left-hemispheric cerebellar activation in a cluster extending from lobule VI to lobule V (compared to TD controls). Following angry face presentation, adolescents with ASD exhibited only midline cerebellar activation (posterior IX vermis). Our findings indicate an early (125-175 ms) overactivation in cerebellar activity only for happy faces and a later overactivation for both happy (250-450 ms) and angry (250-350 ms) faces in adolescents with ASD. The prioritized hemispheric activity (happy faces) could reflect the promotion of a more flexible and adaptive social behavior, while the latter midline activity (angry faces) may guide conforming behavior.