Daniel S, Renwick M, Chau VQ, Datta S, Maddineni P, Zode G, Wade EM, Robertson SP, Petroll MW, Hulleman JD.
Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity. J Mol Med (Berl) 2020;98(11):1639-1656.
AbstractFibulin-3 (F3) is an extracellular matrix glycoprotein found in basement membranes across the body. An autosomal dominant R345W mutation in F3 causes a macular dystrophy resembling dry age-related macular degeneration (AMD), whereas genetic removal of wild-type (WT) F3 protects mice from sub-retinal pigment epithelium (RPE) deposit formation. These observations suggest that F3 is a protein which can regulate pathogenic sub-RPE deposit formation in the eye. Yet the precise role of WT F3 within the eye is still largely unknown. We found that F3 is expressed throughout the mouse eye (cornea, trabecular meshwork (TM) ring, neural retina, RPE/choroid, and optic nerve). We next performed a thorough structural and functional characterization of each of these tissues in WT and homozygous (F3) knockout mice. The corneal stroma in F3 mice progressively thins beginning at 2 months, and the development of corneal opacity and vascularization starts at 9 months, which worsens with age. However, in all other tissues (TM, neural retina, RPE, and optic nerve), gross structural anatomy and functionality were similar across WT and F3 mice when evaluated using SD-OCT, histological analyses, electron microscopy, scotopic electroretinogram, optokinetic response, and axonal anterograde transport. The lack of noticeable retinal abnormalities in F3 mice was confirmed in a human patient with biallelic loss-of-function mutations in F3. These data suggest that (i) F3 is important for maintaining the structural integrity of the cornea, (ii) absence of F3 does not affect the structure or function of any other ocular tissue in which it is expressed, and (iii) targeted silencing of F3 in the retina and/or RPE will likely be well-tolerated, serving as a safe therapeutic strategy for reducing sub-RPE deposit formation in disease. KEY MESSAGES: • Fibulins are expressed throughout the body at varying levels. • Fibulin-3 has a tissue-specific pattern of expression within the eye. • Lack of fibulin-3 leads to structural deformities in the cornea. • The retina and RPE remain structurally and functionally healthy in the absence of fibulin-3 in both mice and humans.
Dohlman JC, Habib LA, Cunnane ME, Yoon MK.
Subperiosteal Masqueraders as Compared to Subperiosteal Abscess: Contrasting Clinical Presentation and Radiographic Densities. Ophthalmic Plast Reconstr Surg 2020;36(6):596-600.
AbstractPURPOSE: Subperiosteal orbital lesions are most commonly abscesses secondary to sinusitis but, in rare cases, may represent other processes. Here, the authors compare the clinical and radiographic presentation of subperiosteal abscesses and alternate subperiosteal processes ("masqueraders") in an effort to establish distinguishing preoperative diagnostic criteria. METHODS: A retrospective chart review of cases of subperiosteal orbital lesions that underwent surgical intervention over a 3-year period was performed. The medical records of 6 cases of subperiosteal masqueraders and 6 cases of abscesses were reviewed for the clinical course, imaging (including radiographic density of lesions), and pathology. Clinical and radiographic features of the 2 groups were compared. RESULTS: All cases presented with orbital signs on exam. Fever and leukocytosis were absent in the masquerader group and present in 3 patients from the abscess group. Common radiographic findings in both groups included a rim-enhancing convex mass along the orbital wall and adjacent sinus opacification, often with bony dehiscence. Of the masqueraders, the final diagnosis was hematoma in 3 cases, mucocele in 1, and malignancy in 2. The difference between the mean radiodensity of the subperiosteal abscesses, 38 ± 5 Hounsfield units (95% CI, 34-42), as compared with the average radiodensity of the masqueraders, 71 ± 5 Hounsfield units (95% CI, 67-75), was significant (p = 0.042). Comparing radiodensity of the orbital lesion to adjacent sinus lesions and metastatic lesions elsewhere was also informative in establishing the diagnosis. CONCLUSIONS: Radiographic features, particularly radiodensity, may help distinguish subperiosteal abscesses from other lesions and aid in preoperative diagnosis and management.
Dohlman JC, Wolkow N, Yoon MK.
Sequential Bilateral Subperiosteal Hematomas. Ophthalmic Plast Reconstr Surg 2020;36(6):e162.
Dohlman JC, Cestari DM, Freitag SK.
Orbital disease in neuro-ophthalmology. Curr Opin Ophthalmol 2020;31(6):469-474.
AbstractPURPOSE OF REVIEW: Orbital disease represents a diverse spectrum of pathology and can result in a variety of neuro-ophthalmic manifestations. The aim of this review is to provide updates on recent advances in our understanding of orbital disease secondary to thyroid eye disease, myositis, IgG4-related disease, sarcoidosis, granulomatosis with polyangiitis and various tumours. RECENT FINDINGS: With regards to thyroid eye disease, there have been recent advances in the development of steroid-sparing therapies, new modalities for objectively monitoring disease activity and increased understanding of the role of environmental risk factors. There has been interest in characterizing the clinical course and underlying mechanism of optic nerve disease secondary to orbital disorders, which has led to advances in how we monitor for and prevent permanent vision loss. Increased knowledge of orbital tumour subtype histopathology and the development of novel classification systems has had prognostic value and aided medical decision-making. SUMMARY: Orbital disease occurs secondary to a wide variety of diseases and can lead to neuro-ophthalmic manifestations with significant morbidity. Advances in our understanding of different subtypes of orbital disease have improved our ability to treat these potentially debilitating conditions.
Douglas VP, Douglas KA, Cestari DM.
Optic nerve sheath meningioma. Curr Opin Ophthalmol 2020;31(6):455-461.
AbstractPURPOSE OF REVIEW: Optic nerve sheath meningiomas (ONSMs) are rare benign tumors of the anterior visual pathway which present with slowly progressive and painless vision loss and account for approximately 2% of all orbital tumors. This article provides an overview as well as an update on the ONSMs with regards to cause, epidemiology, clinical presentation, diagnosis, and management in adults and pediatric population. RECENT FINDINGS: The clinical presentation and prognosis of ONSMs can vary and largely depend on the location of tumor as well as the histologic type. Overall, the diagnosis is based on clinical presentation, examination, and neuroimaging findings. Nevertheless, delays in diagnosis or misdiagnosis are not uncommon and can result in higher morbidity rates. Recent advances in diagnostic as well as more effective and less-invasive treatment options are discussed in this review. SUMMARY: ONSMs are a rare cause of slowly progressive and inexorable visual loss. Although ONSM diagnosis depends on the characteristic clinical and radiologic findings, prompt diagnosis, and appropriate management is critical for favorable visual outcomes. Thus, current focus is optimizing diagnostic as well-treatment methods for patients with ONSMs.