A genotype-phenotype comparison of ADAMTSL4 and FBN1 in isolated ectopia lentis.

PURPOSE: To describe the genotype-phenotype relationship of a cohort of consecutive patients with isolated ectopia lentis (EL) secondary to ADAMTSL4 and FBN1 mutations. METHODS: Patients underwent detailed ocular, cardiovascular, and skeletal examination. This was correlated with Sanger sequencing of ADAMTSL4 and FBN1 genes. RESULTS: Seventeen patients were examined, including one with ectopia lentis et pupillae. Echocardiography and skeletal examination revealed no sign of systemic disorders associated with EL, in particular Marfan syndrome (MFS). Nine patients (52.9%) were found to have mutations in ADAMTSL4, including four novel nonsense mutations. Four patients (25%) were found to have novel FBN1 mutations, not previously reported as causing classical Marfan syndrome. One additional patient was found to have an FBN1 mutation previously reported in classical MFS. Four patients (25%) were found to have no mutations in either gene. Median age of diagnosis of EL was 35 years in patients with FBN1 mutations and 2 years in patients with ADAMTSL4 mutations (P < 0.01). Mean axial length was 22.74 mm (95% confidence interval [CI]: 21.3-24.2) (FBN1) and 27.54 mm (95% CI: 24.2-30.9) (ADAMTSL4) (P < 0.01). Other ophthalmic features, including corneal thickness and power, foveal thickness, visual acuity, and direction of lens displacement, were similar for both groups. CONCLUSIONS: ADAMTSL4 is the most important known causative gene in isolated EL. Mutations in ADAMTSL4 appear to cause earlier manifestation of EL and are associated with increased axial length as compared to FBN1. We suggest that ADAMTSL4 be screened in all patients with isolated EL and that physicians be vigilant for the more severe ocular phenotype associated with mutations in this gene.

Acute glaucoma secondary to angle obstruction by triamcinolone crystals.

PURPOSE: To present a case of acute glaucoma secondary to massive transit of triamcinolone acetonide into the anterior chamber in a pseudophakic, vitrectomized eye following intravitreal injection for treatment of cystoid macular edema. SETTING: Manchester Royal Eye Hospital. METHOD: Case study. CONCLUSION: In vitrectomized eyes with open posterior capsule receiving high dose intravitreal triamcinolone, it is prudent to perform pressure check within a week of injection.

Severe heparin-induced thrombocytopenia: when the obvious is not obvious, a case report.

Thrombocytopenia commonly occurs in hospitalized patients, particularly critically ill patients. We present an exemplifying case of severe heparin-induced thrombocytopenia (HIT) in an effort to solidify its high priority in the differential diagnosis of thrombocytopenia. A 75-year-old female underwent cardiac surgery with intraaortic balloon pump (IABP) placement. A platelet count drop to 25 x 10(9)/L by the third postoperative day was attributed to the IABP, which was removed. Her thrombocytopenia remained refractory to multiple platelet transfusions over several days. Right hand cyanosis then developed, attributed to a right radial arterial catheter, which was removed. All toes and fingers then showed severe ischemic changes. Ten days after the initial platelet count drop, a critical care specialist new to the treating team suspected HIT. Heparin exposure was stopped and argatroban was initiated. A HIT antibody test was subsequently strongly positive. The patients thrombocytopenia gradually resolved. No additional thromboses occurred during a 27-day intensive care unit stay. This case underscores the need for vigilance in suspecting HIT in patients with thrombocytopenia and recent heparin exposure. To avoid catastrophic outcomes in such patients, heparin should be stopped and alternative anticoagulation should be initiated, at least until HIT is excluded.