Variants in myelin regulatory factor (MYRF) cause autosomal dominant and syndromic nanophthalmos in humans and retinal degeneration in mice.

Nanophthalmos is a rare, potentially devastating eye condition characterized by small eyes with relatively normal anatomy, a high hyperopic refractive error, and frequent association with angle closure glaucoma and vision loss. The condition constitutes the extreme of hyperopia or farsightedness, a common refractive error that is associated with strabismus and amblyopia in children. NNO1 was the first mapped nanophthalmos locus. We used combined pooled exome sequencing and strong linkage data in the large family used to map this locus to identify a canonical splice site alteration upstream of the last exon of the gene encoding myelin regulatory factor (MYRF c.3376-1G>A), a membrane bound transcription factor that undergoes autoproteolytic cleavage for nuclear localization. This variant produced a stable RNA transcript, leading to a frameshift mutation p.Gly1126Valfs*31 in the C-terminus of the protein. In addition, we identified an early truncating MYRF frameshift mutation, c.769dupC (p.S264QfsX74), in a patient with extreme axial hyperopia and syndromic features. Myrf conditional knockout mice (CKO) developed depigmentation of the retinal pigment epithelium (RPE) and retinal degeneration supporting a role of this gene in retinal and RPE development. Furthermore, we demonstrated the reduced expression of Tmem98, another known nanophthalmos gene, in Myrf CKO mice, and the physical interaction of MYRF with TMEM98. Our study establishes MYRF as a nanophthalmos gene and uncovers a new pathway for eye growth and development.

Orbital and periorbital myofibromas in childhood: two case reports.

PURPOSE: Infantile myofibromatosis is an uncommon tumor that occurs rarely in the periorbit and orbit. This article reports two cases of infantile myofibromatosis of the orbital adnexa and describes the associated clinical, histopathologic, and immunohistochemical findings. DESIGN: Two retrospective, interventional case reports with clinicopathologic correlation. INTERVENTION: Treatment consisted of excision of the tumors. MAIN OUTCOME MEASURES: Histologic and immunohistochemical evaluation and clinical evaluation for tumor recurrence. RESULTS: The first patient was a newborn male with a large tumor extending from his eyelid that was excised at day 2 of life. Histologic and immunohistochemistry analyses were used to make a diagnosis of infantile myofibromatosis. He remains disease free at age 7 years. The second case was a 6-year-old boy with a 1-month history of proptosis resulting from an orbital mass. Incisional biopsy revealed a tumor consistent with infantile myofibromatosis. He remains tumor free 12 months after complete gross surgical resection. CONCLUSIONS: Infantile myofibromatosis is an uncommon tumor that is rare in the orbit. Differential diagnosis can be difficult based solely on histologic analysis. Immunohistochemistry evaluation demonstrating cytoplasmic actin filaments within neoplastic spindle cells confirms the diagnosis. As soon as the diagnosis is made, chest and abdominal imaging is of value to define the prognosis and to direct further treatment. After the diagnosis of nonvisceral infantile myofibromatosis, complete gross resection, if possible, is the treatment of choice.

Graft contraction: a comparison of acellular dermis versus hard palate mucosa in lower eyelid surgery.

PURPOSE: To compare graft contraction rates of acellular dermis versus hard palate mucosa when used as free spacer grafts in lower eyelid surgery and to provide clinical outcome data. METHODS: A prospective, nonrandomized clinical trial involving the placement of 19 spacer grafts in the lower eyelids of 14 patients was performed. Indications for spacer graft placement included lower eyelid retraction and mildly contracted socket. Patients with lower eyelid retraction also underwent an endoscopic subperiosteal midface lift. For all procedures, the height of each graft was measured during and after surgery. The amount of contraction was measured for each graft, and a mean was calculated for each spacer material. The clinical success was evaluated for all procedures, based on improvement of the functional concern being addressed. RESULTS: The mean graft contraction rate was 57% for the acellular dermis and 16% for the hard palate mucosal grafts (P <0.005). Of the 7 procedures using acellular dermis for lower eyelid retraction, 6 were considered a success, and 1 was considered a partial success. Of the 6 procedures using hard palate for lower eyelid retraction, 5 were considered a success, and 1 was considered a failure unrelated to the graft. Of the 5 procedures with acellular dermis used for mildly contracted socket, 2 were considered a success, 2 were considered a partial success, and 1 was considered a failure because of graft contraction. The one case using hard palate for mildly contracted socket was considered a success. CONCLUSIONS: Acellular dermis contracts significantly more than hard palate mucosa when used as a lower eyelid spacer graft. Acellular dermis and hard palate mucosa were both associated with a high rate of clinical success in all categories except for patients with a mildly contracted socket who received acellular dermis; more than 60% of these patients (n=5) had only partial success or failure caused by graft contraction.

Müller muscle-conjunctival resection: effect on tear production.

PURPOSE: To study the effect of upper eyelid ptosis repair by Müller muscle-conjunctival resection on tear production. METHODS: The authors retrospectively reviewed the charts of 174 patients who underwent ptosis repair by Müller muscle-conjunctival resection at the Casey Eye Institute between October 1996 and August 2001. After exclusions for insufficient data and confounding ocular morbidities, the charts of 38 patients, consisting of 71 ptosis repair surgeries, were analyzed. A single surgeon performed the same procedure on all patients. All subjects underwent Schirmer testing before ptosis repair and again during the period between 6 weeks to 18 months after surgery. Patients responded to questions pertaining to dry eye symptoms during preoperative and postoperative visits. RESULTS: No statistically significant change in tear production (as measured by Schirmer strip testing) associated with ptosis correction by Müller muscle-conjunctival resection was observed. Before surgery, 34% (24 of 71) of eyes measured dry before ptosis repair. This ratio remained unchanged on long-term follow-up. A transient increase in dry-eye symptoms was reported in at least one eye of 29% (11 of 38) of patients in the immediate postoperative period (<2 weeks). On long-term follow-up, a persistent increase in dry-eye symptoms or new diagnosis of dry eye was observed in at least one eye of 16% (6/38) of patients, whereas 13% (5/38) of patients noticed diminution of their presurgical dry eye symptoms. CONCLUSIONS: Upper eyelid ptosis repair by Müller muscle-conjunctival resection had no significant effect on tear production as measured by Schirmer testing. Subjective dry-eye symptoms transiently increased in the immediate postoperative period but resolved frequently by the late follow-up period.

Endoscopic subperiosteal midface lift: surgical technique with indications and outcomes.

PURPOSE: To review the surgical technique of the endoscopic subperiosteal midface lift and present our clinical outcome in 22 consecutive patients. METHODS: We retrospectively evaluated the clinical outcomes of 39 endoscopic subperiosteal midface lifts in 22 consecutive patients. Of the 39 sides, 21 had a lower eye conjunctival spacer graft inserted (15 hard palate mucosal graft, 6 AlloDerm). The success of the procedure was graded based on the aesthetic and functional results. Subjective and objective assessments were made using history, examination, and photos. RESULTS: Results for the clinical outcome were graded as excellent, good, fair, or poor. Among the 39 sides, indications for the procedure included facial rejuvenation (41%), postblepharoplasty lower eyelid retraction (26%), eyelid retraction secondary to midfacial ptosis (15%), severe cicatricial ectropion (13%), and paralytic ectropion secondary to 7th nerve palsy (5%). The operating surgeons evaluated the clinical outcome as "excellent" in 24 sides (61%), "good" in 10 sides (26%), "fair" in 2 sides (5%), and "poor" in 3 sides (8%). The procedure was successful at increasing malar projection, improving lower eyelid fullness, and elevating the lower eyelid in cases of lower eyelid retraction. The procedure was less effective in decreasing the prominence of the deep nasolabial fold. CONCLUSIONS: The endoscopic subperiosteal midface lift is an effective method for elevating the midface. A more youthful appearance is achieved with the procedure, and when necessary, recruitment of anterior lamella allows elevation of the lower eyelid to correct retraction.