Major Article Histopathological features and satellite cell population characteristics in human inferior oblique muscle biopsies: clinicopathological correlation Ata Baytaro glu, MD, a Hande Taylan S ¸ ekero glu, MD, PhD, a Kadriye Erkan Turan, MD, a and Diclehan Orhan, MD b PURPOSE To investigate the correlation between clinical characteristics and histopathological and immunohistochemical features of inferior oblique muscles in patients with primary and secondary inferior oblique overaction. METHODS Inferior oblique muscle specimens of patients who underwent inferior oblique–weakening procedures for primary or secondary inferior oblique overaction were recruited. Subjects were mainly divided into two groups, each of which was further divided into two sub- groups: group 1 included patients with primary inferior oblique overaction (subgroups, in- fantile esotropia vs acquired V-pattern esotropia), and group 2 included patients with secondary inferior oblique overaction (subgroups, congenital vs acquired trochlear nerve palsy). Inferior oblique overaction was graded between 0-4. Histopathologic changes, such as angular fibers, endo- and perimysial fibrosis, and vacuolization were categorized from mild to severe. Immunohistochemical markers Pax7, NCAM, and MyoD1 were used to detect satellite cells, a unique stem cell population in muscles presumably respon- sible from myofiber regeneration and maintenance, and their activity. Results were re- ported as stained cells per cross-section ratio. RESULTS A total of 51 patients were included: 36 in group 1 and 15 in group 2. Satellite cell distri- bution and activity was significantly higher in group 1 (P \ 0.001). The angular fiber count and the degree of perimysial fibrosis was higher in the secondary group (P \ 0.001 and P 5 0.01, resp.). There was no correlation between clinical amount of inferior oblique mus- cle overaction and immunohistochemical markers. CONCLUSIONS The differences in immunohistochemical parameters supported with histopathological changes between different strabismus etiologies imply that satellite cell population behavior varies among strabismus types. ( J AAPOS 2020;-:1.e1-6) S trabismus is a large group of diseases, with a preva- lence of 2%-4%. 1,2 An underlying central nervous system anomaly is detected in only 12% of all stra- bismus cases. 1,3 Subgroups of strabismus observed without any other pathology include entities such as infantile eso- tropia and primary inferior oblique muscle over action (IOOA), with a prevalence of 1%-5%. 1,3 IOOA, which is observed as hyperelevation of the eye in adduction, occurs in approximately 19% of these strabismus types. Parks divided it into two etiological groups: primary and second- ary. 4 Primary IOOA is usually bilateral, asymmetric, and without any muscle paralysis, whereas secondary IOOA de- velops secondary to superior oblique muscle paralysis on the same side. The high frequency of IOOA in sensory stra- bismus secondary to vision loss in one eye often raises the question as to whether the mechanism initiating this over- action is a primary muscle dysfunction or secondary neuro- genic mechanism. 5 Secondary IOOA is detected in paralysis of the trochlear nerve, and 70% of this group con- sists of pediatric cases, especially congenital paralysis cases. 3,6 Studies investigating a possible primary muscle pathology that can differentiate between primary and sec- ondary inferior oblique muscle pathologies have shown that different morphological changes (mitochondrial accu- mulation, vacuolization, angular fiber formation) are prominent in different strabismus types, 7 but these studies did not point out a possible effect of stem cell population, which has a unique behavior in extraocular muscles that Author affiliations: a Department of Ophthalmology, Hacettepe University Faculty of Medicine, Ankara, Turkey; b Department of Pediatrics, Pediatric and Perinatal Pathology Unit, Hacettepe University Faculty of Medicine, Ankara, Turkey This work was supported by the Hacettepe University Scientific Research Projects Coordination Unit, Project Number THD-2017-13146. Submitted September 8, 2019. Revision accepted May 19, 2020. Correspondence: Ata Baytaro glu, MD, Aydin State Hospital Ophthalmology Department, Efeler-Aydin, Turkey, 09100 (email: baytaroglua@gmail.com). Copyright Ó 2020, American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved. 1091-8531/$36.00 https://doi.org/10.1016/j.jaapos.2020.05.012 Journal of AAPOS 1.e1