Whole exome sequencing reveals a novel de novo FOXC1 mutation in a patient with unrecognized Axenfeld-Rieger syndrome and glaucoma.

We report the identification of a novel mutation in the fork-head box C1 (FOXC1) gene which occurred de novo in an Italian patient with unrecognized Axenfeld-Rieger syndrome. He was previously diagnosed as having late recognized primary congenital glaucoma at the age of 14 years and was subsequently subjected to multiple surgical interventions due to uncontrolled intraocular pressure and progressive visual field loss. After exclusion of mutations in CYP1B1 and MYOC, trio-whole-exome sequencing revealed de novo in frame deletion in the coding region of the FOXC1 gene (c.407_409delGTC, p.V137del) leading to a deletion of the evolutionary conserved amino acid Valine at position 137 of the protein. Molecular modeling predicted that Val137 deletion impairs FOXC1 DNA-binding capacity and transcriptional activation. Since loss-of-function mutations in FOXC1 are associated with Axenfeld-Rieger syndrome, the genetic findings in combination with re-evaluation of the patient's clinical data resulted in a corrected diagnosis of Axenfeld-Rieger syndrome with developmental glaucoma. We therefore suggest that in addition to CYP1B1 and MYOC, FOXC1 should be included in the genetic analysis of cases with unclear glaucomatous phenotypes to ensure proper diagnosis, adequate treatment and appropriate genetic counseling.

Congenital ptosis and blefarophimosis: retrospective analysis of the effectiveness of correction with levator resection and frontalis suspension.

BACKGROUND: treatment of congenital ptoses and blepharophimoses relies on levator resections and frontalis suspensions. Several techniques of levator resection have been described in literature, some of them include tarsal resections and resections of the Müller muscle. Nevertheless a gold treatment have not been detected yet. Frontalis suspension is performed when levator muscle is not functional or when ptosis is severe. The suspension could be carried out with several materials: ePTFE, silicon rods, poly-propylene, nylon, braided poliester, but the preferable material is considered the autologous fascia lata. AIMS: this study was designate to determine retrospectively if the indications of surgery are correct, considering age, severity of pathology, relapses and complications. An analysis of demographic data and outcomes for each technique is performed. METHODS: in this study we analyze case series of 33 pediatric patients affected by congenital ptosis and blepharophimosis congenital syndrome, surgically treated from 2000 to 2008 in the ophtalmic pediatric surgery department at the Niguarda Hospital of Milan. A literature review was also performed. RESULTS: the mean age at presentation was 4.13. The diagnosis was precocious in most cases and often helped by some recognizable clinical signs: compensatory head posture (48.5%), anisometropia (36.4%), astigmatism (48.5%), strabismus (36.4%) and amblyopia (15.2%). Most of patients was treated with frontalis suspension (57.6%) and their age was significatively lower than patients treated with levator resection. No difference about complications and recurrence was reported between the two techniques. Complications and recurrence amount to 39.4%. CONCLUSION: these results are in line with other studies in literature. A precociuos treatment is able to reduce the incidence of amblyopia from 34% to 8%. The choice of the treatment (resection Vs suspension) has to consider the age of the patient, the severity of ptosis and avaibility of fascia lata. Nevertheless no significative difference in outcomes have been demonstrated between the two techniques.

Comparison of lodoxamide 0.1% ophthalmic solution and levocabastine 0.05% ophthalmic suspension in vernal keratoconjunctivitis.

PURPOSE: To compare the clinical efficacy and safety of lodoxamide 0.1% ophthalmic solution with levocabastine 0.05% ophthalmic suspension, each given four times daily (QID) for three months to patients with vernal keratoconjunctivitis (VKC). METHODS: The study was conducted multinationally according to a triple-masked parallel design in 95 VKC patients, with assessments at baseline then monthly during the three months of treatment. The primary efficacy variables were a Physician's Clinical Judgement Scale and a Patient's Overall Judgement Scale of improvements from baseline. Signs and symptoms of VKC were also assessed. RESULTS: Both primary efficacy variables showed significantly greater overall improvement of VKC from baseline with lodoxamide than levocabastine. The superiority of lodoxamide was demonstrated by the Physician's Clinical Judgement Scale at months 2 and 3, with a trend, at month 1, and by the Patient's Overall Judgement Scale at months 1, 2 and 3. All signs and symptoms of VKC improved significantly from baseline at all time points, regardless of treatment (p<0.001). However, relative to levocabastine, conjunctival discharge, photophobia and lacrimation were significantly reduced by lodoxamide at months 1, 2 and 3, itching at months 2 and 3, and bulbar conjunctiva at month 3. The temporal improvement of superior tarsal papillae did not differ significantly between treatments. Both were well tolerated. CONCLUSIONS: Lodoxamide 0.1% and levocabastine 0.05% eye drops, instilled four times daily for three months, were effective, safe and well tolerated by patients with VKC, but lodoxamide was significantly superior to levocabastine.

Papillitis as an onset sign of Leber's hereditary optic neuropathy: a case report.

Leber's hereditary optic neuropathy is a maternally transmitted disease resulting from a point mutation in mitochondrial (mt) DNA. In this report we describe a case of Leber's disease with typical clinical findings but atypical ophthalmoscopic presentation. A 14-year-old boy developed severe loss of vision acuity in the left eye, with only partial recovery, followed 4 months later by the same symptoms in the right eye. Fundoscopic examination showed hyperemic papilla on the right eye and optic disc pallor on the left eye. Polymerase chain reaction analysis of lymphocytic mt-DNA revealed a point mutation at 11778. Leber's disease should be considered in young patients (not always male) with sudden visual loss and simple papillary involvement at fundoscopic examination but without the typical telangiectatic microangiopathy.