Next generation sequencing uncovers a missense mutation in COL4A1 as the cause of familial retinal arteriolar tortuosity.

OBJECTIVES: Our aim was to determine the molecular cause of autosomal dominant familial retinal arteriolar tortuosity (FRAT) in a family with three affected subjects. MATERIAL AND METHODS: Ophthalmologic evaluation included determination of best-corrected visual acuity (BCVA), slit-lamp and dilated fundus inspection, applanation tonometry, fundus photography, and fluorescein retinal angiography (FA). Molecular methods included whole exome sequencing analysis and Sanger sequencing validation of putative causal mutation in DNA from affected individuals. RESULTS: Typical signs of familial retinal arteriolar tortuosity were observed in all three patients. Exome sequencing identified a heterozygous c.1528G > A (p. Gly510Arg) mutation in COL4A1. Sanger sequencing confirmed that all three patients harbored the same pathogenetic mutation in COL4A1. The p. Gly510Arg variant in COL4A1 was absent in DNA from an available unaffected daughter, from a set of control alleles, and from publicly available databases. CONCLUSIONS: The molecular basis of familial retinal arteriolar tortuosity was identified for the first time, thus expanding the human phenotypes linked to COL4A1 mutations. Interestingly, the COL4A1 p.Gly510Arg mutation has been previously identified in a family with HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and Cramps), a multisystemic disease featuring retinal arteriolar tortuosity. No cerebral, neurologic, renal, cardiac or vascular anomalies were recognized in the pedigree described here. These data indicate that identical mutations in COL4A1 can originate both eye-restricted and systemic phenotypes.

INTRARETINAL HUMAN AMNIOTIC MEMBRANE AFTER MACULAR HOLE REPAIR.

PURPOSE: To describe a unique complication of macular hole repair surgery using a subretinal human amniotic membrane plug. METHODS: Retrospective, interventional case report. RESULTS: A 71-year-old man presented with a chronic full-thickness macular hole in his left eye. Conventional 23-gauge pars plana vitrectomy with internal limiting membrane peeling and implantation of a subretinal human amniotic membrane plug was performed. In the postoperative period, centripetal growth of external retinal layers was observed under the plug. Six months after the surgery, the human amniotic membrane plug was completely integrated into the retina. CONCLUSION: This is the first reported case of intraretinal integration of a human amniotic membrane plug after macular hole repair surgery.

Comparing the in vitro efficacy of chlorhexidine and povidone-iodine in the prevention of post-surgical endophthalmitis.

BACKGROUND: Intravitreal injections are a common ophthalmologic procedure. While infections following these injections are rare, they can lead to endophthalmitis, with potentially serious consequences. Various methods have been proposed to prevent endophthalmitis, including the use of antisepsis and antibiotics in patient preparation. PURPOSE: To evaluate the antiseptic efficacy of aqueous chlorhexidine (CHX) and povidone-iodine (PI) when used alone and in combination with lidocaine gel (LG) in vitro. METHODS: Two independent experimental trials were conducted. The first trial determined the minimum inhibitory concentrations (MICs) and the minimum bactericidal concentrations (MBCs) of CHX and PI against six bacterial strains. The second trial evaluated the bactericidal efficacy of the antiseptic agents (CHX 0.1% and PI 5%) and their combination with LG against the same bacterial strains. RESULTS: CHX was more effective than PI in reducing the number of colonies forming units (cfus) of the tested bacteria. The order in which the antiseptic and LG were administered affected their effectiveness, with CHX administered before LG resulting in greater reduction of bacterial growth. CONCLUSIONS: CHX 0.1% is more effective than PI 5% as an antiseptic agent. Application of CHX and PI prior to the use of lidocaine gel results in a more effective reduction of microorganisms.

A novel mutation confirms MFRP as the gene causing the syndrome of nanophthalmos-renititis pigmentosa-foveoschisis-optic disk drusen.

PURPOSE: To describe the clinical and genetic characteristics of the second family with a recently described recessive syndrome characterized by posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen. DESIGN: Observational case report. METHODS: Three affected subjects and one healthy sibling from a consanguineous marriage from Spain were studied. Complete ophthalmologic examinations including A- and B-mode ultrasonography (US), electroretinography (ERG), fluorescein retinal angiography (FA), and optical coherence tomography (OCT) were performed in each individual. Genetic analysis included polymerase chain reaction amplification and direct nucleotide sequencing of the complete MFRP gene. RESULTS: All three affected siblings had bilateral shortening of the posterior ocular segment associated with high hyperopia and normal anterior segment dimensions. Best-corrected visual acuity ranged from 20/200 to 20/60. Funduscopy, ERG, and FA were compatible with retinitis pigmentosa, and B-mode ultrasound showed optic disk drusen. OCT analysis revealed outer retinal layer schisis with absence of foveal pit. Inheritance of this syndrome followed an autosomal recessive pattern. Molecular analysis revealed a novel homozygous 1-bp deletion (c.498delC) in exon 5 of MFRP, predicting a prematurely truncated protein (P166fsX190). A healthy sister demonstrated to be a carrier of the mutation. CONCLUSIONS: We confirmed that the syndrome of posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen constitutes a distinct autosomal recessive entity. The novel frameshift mutation identified in the family described here validates MFRP as the gene responsible for this particular disease, which characteristically involves structures located at the posterior segment of the eye.

Acute-Onset Endophthalmitis Caused by Alloiococcus otitidis following a Dexamethasone Intravitreal Implant.

PURPOSE: To report the first case of acute endophthalmitis caused by Alloiococcus otitidis after a dexamethasone intravitreal implant. METHODS: A 74-year-old female was treated with intravitreal Ozurdex(®) in her left eye for central retinal vein occlusion (CRVO). Best-corrected visual acuity (BCVA) in the eye was 4/20. Intravitreal injection was uneventful. At 48 h after injection, she developed ocular pain and visual acuity had dropped to light perception. Endophthalmitis associated with intravitreal injection was suspected. RESULTS: The patient did not show a favorable clinical response following systemic, intravitreal, and topical fortified antibiotics. We then performed a vitreous biopsy and removed the Ozurdex implant by pars plana vitrectomy. A vitreous culture was positive for A. otitidis. At the 2-month follow up, no inflammation was observed, but due to CRVO and probably aggravated by endophthalmitis, the fundus showed macular fibrosis. The final BCVA was finger counting at 30 cm in her left eye. CONCLUSIONS: In cases of an intravitreal implant associated with endophthalmitis, we recommend removal of the device because it may act as a permanent reservoir of organisms if it remains in the vitreous cavity.

Topical azithromycin or ofloxacin for endophthalmitis prophylaxis after intravitreal injection.

BACKGROUND: The number of patients who have undergone intravitreal injections has increased enormously in recent years, but a consensus is still lacking on prophylaxis for endophthalmitis. The aim of this prospective, observational study was to evaluate the prophylactic effect of azithromycin eye drops versus ofloxacin eye drops. METHODS: The study was conducted in five hospitals in Spain and included all patients undergoing intravitreal injections of triamcinolone, bevacizumab, ranibizumab, or pegaptanib over one year. Patients received azithromycin 15 mg/g eye drops (twice daily on the day prior to injection and for another 2 days) or ofloxacin 3 mg/g eye drops (every 6 hours on the day prior to injection and for another 7 days). RESULTS: In the azithromycin group, there were 4045 injections in 972 eyes of 701 patients. In the ofloxacin group, there were 4151 injections in 944 eyes of 682 patients. There were two cases of endophthalmitis (0.049%) in the azithromycin group and five (0.12%) in the ofloxacin group. The odds ratio of presenting with endophthalmitis in the ofloxacin group compared with the azithromycin group was 2.37 (95% confidence interval [CI] 1.32-3.72, P < 0.001). There were two cases of noninfectious uveitis after triamcinolone injection in the azithromycin group (0.049%) and two (0.048%) in the ofloxacin group; no significant differences were observed (odds ratio 0.902, 95% CI 0.622-1.407, P = 0.407). Conjunctival hyperemia was observed in 12 cases in the azithromycin group and none in the ofloxacin group. CONCLUSION: The risk of endophthalmitis was significantly greater with ofloxacin than with azithromycin. These findings provide a valuable addition to the ever-increasing pool of information on endophthalmitis prophylaxis after intravitreal injection, although further large-scale studies are required to provide definitive conclusions.