Scott M. Goldstein

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

The male eyebrow: a topographic anatomic analysis.

Purpose: To study and quantify the topographic anatomy of the male eyebrow and its 3-dimensional relation, based on age and location, relative to the eye and the supraorbital rim. Methods: A prospective cohort of male patients seen for routine ophthalmic evaluation age 10 years and older had several eyebrow measurements incorporated in the examination. The presence or absence of brow ptosis was noted on the basis of observation. The location of the eyebrow relative to the center of the pupil, the lateral canthus, and the depth of the supraorbital rim was measured. The data were subjected to statistical analysis. Results: The study included 444 eyebrows of 222 patients ranging in age from 10 to 86 years, with a mean age of 46.75 years. The incidence of brow ptosis was 7.4%. The mean distance between the lateral canthus and inferior brow (LIBD) was 11.23 mm. The mean distance between the pupil and the inferior brow and the superior brow border was 11.15 mm (PIBD) and 19.8 mm (PSBD), respectively. Statistical analysis demonstrated that the mean brow position did not vary with age. However, there was a significant negative correlation between the position of the eyebrow and the depth of the superior sulcus below the supraorbital rim (correlation coefficient, 0.431 for PIBD and depth and 0.381 for LIBD and depth, respectively). Deeper-set eyes had lower brow position. Conclusions: The male eyebrow sits along the supraorbital ridge and has a flat contour. In men without frank brow ptosis, the eyebrow position relative to the pupil and the lateral canthus does not significantly fall with age despite the periocular changes associated with aging. However, 3-dimensional analysis demonstrates that individuals with deep-set eyes have a lower positioned eyebrow then those with a more shallow depth below the supraorbital rim. These findings are helpful in surgical management of the eyelid-eyebrow continuum. The age-related changes in the eyebrow area should be thought of as a 3-dimensional construct with collapse of the structure and not simply descent of the eyebrow.

Orbital presentation of posttransplantation lymphoproliferative disorder: A small case series

OBJECTIVE To describe a small series of patients with orbital presentation of posttransplantation lymphoproliferative disorder (PTLD). DESIGN Retrospective, interventional case series. PARTICIPANTS Three patients with orbital presentation of histologically diagnosed PTLD. METHODS Review of medical records. MAIN OUTCOME MEASURES Measured parameters included vision, proptosis, and tumor extent. RESULTS Three cases of orbital PTLD are described. In two of the cases, the tumor initially demonstrated orbital signs and symptoms, whereas in the third case, orbital and systemic signs were synchronous. Two of three patients had disseminated disease discovered at the time of presentation. One adult patient had synchronous presentation of PTLD in the orbit and prostate. One pediatric patient had tumor dissemination to the liver at the time of presentation. The PTLD tumors were classified histologically as diffuse large cell lymphoma of monomorphic or immunoblastic type in all three cases. Treatment included local irradiation, decreased immunosuppression, and antilymphocyte monoclonal antibodies. CONCLUSIONS Orbital presentation is a rare manifestation of PTLD. However, ophthalmologists must consider this diagnosis carefully in organ transplant recipients with subtle orbital signs and symptoms at presentation. Early detection may alter prognosis. In each case presented, the diagnosis was established via lesion biopsy and subsequent histologic or flow cytometric evaluation, or both.

Alveolar rhabdomyosarcoma masquerading as embryonal subtype: the value of modern molecular diagnostic testing.

A 3-year-old child presented with a history of conjunctivitis in her OS. She had hyperglobus of the OS and a palpable mass in the left inferior orbit. An urgent MRI revealed an enhancing mass in the left orbit. The patient underwent an incisional biopsy with pathologic assessment most consistent with embryonal rhabdomyosarcoma. However, subsequent molecular genetic testing of the biopsy specimen was positive for the PAX3/PAX7-FKHR chimeric gene, indicating the tumor was actually an alveolar rhabdomyosarcoma. The patient received a more intensive chemotherapy regimen and also was treated with proton-beam radiotherapy. After chemotherapy and proton irradiation, the patients tumor shrank considerably, and she remained in remission at over 3 years of follow up. This patient illustrates the new tools at the disposal of the orbital specialist including molecular genetic testing and proton-beam irradiation to diagnose and treat orbital rhabdomyosarcoma.

Diesel fuel injury to the orbit.

A 48-year-old man was seen in the Wills Eye Institute emergency room for pain and decreased vision after having a diesel engine fuel cylinder explosion in his face. Clinical examination showed proptosis, decreased extraocular motility, and increased intraocular pressure; CT scan imaging revealed hypodense areas within the orbit. His orbital signs rapidly worsened despite aggressive antibiotics, steroids, and surgical intervention. Two orbitotomies revealed diesel fuel infiltration of the intraconal and extraconal spaces that proved impossible to evacuate completely. The patient ended up losing vision from an intense chemical cellulitis with subsequent orbital compartment syndrome and optic neuropathy. This case highlights the severity of orbital chemical injuries and their variable prognoses despite aggressive management.

A Hyalinized Trichilemmoma of the Eyelid in a Teenager.

A 16-year-old African American male, the youngest patient to date, presented with a well-circumscribed upper eyelid lesion. On excision, the dermal nodule was contiguous with the epidermis, displayed trichohyalin-like bodies in an expanded outer root sheath, and was composed chiefly of small cellular clusters separated by a prominent network of periodic acid Schiff -positive hyaline bands of basement membrane material. The tumor cells were positive for high molecular weight cytokeratins (CK) 5/6, CK14, and CK34βE12 and were negative for CK7, carcinoembryonic antigen and epithelial membrane antigen. Negative S100, glial fibrillary acidic protein, and smooth muscle actin immunoreactions ruled out a myoepithelial lesion. The Ki-67 proliferation index was <10%. The diagnosis was a hyalinized trichilemmoma, contrasting with the more common lobular type. As an isolated lesion, trichilemmoma does not portend Cowden syndrome.

Pediatric Eyelid and Adnexal Trauma

When confronted with trauma in the pediatric population, there are challenges differing from the adult patient. The mechanism of trauma varies and can be bizarre in nature, testing the skills of the surgeon in both diagnosis and treatment. Examination may be difficult, making accurate diagnosis challenging. Animal bites and unusual projectiles are found more frequently in children, often resulting in an injury pattern involving multiple aspects of the eyelid and adnexa. The surgeon must also take into consideration anatomic difference in both size and proportion. The additional risk for occlusion amblyopia may limit options available during complex repairs and postoperative care. This chapter discusses the evaluation and management of pediatric lid and adnexal trauma in detail. Examples in clinical and surgical settings help to highlight the principles.