AUTOSOMAL DOMINANT MÜLLER CELL SHEEN DYSTROPHY: Clinical, Histopathologic, and Genetic Assessment in an Extended Family With Long Follow-Up.

BACKGROUND: Autosomal dominant Müller cell dystrophy is a rare condition we described in 1991. It is characterized by a striking sheen appearance on the retinal surface with progressive retinal changes leading to disorganization and atrophy with a decreased b-wave electroretinograms. MATERIALS AND METHODS: We examined 45 members of a 4-generation family. Fifteen subjects from three generations were found with the disease, without gender predilection. Seven patients underwent ophthalmic examination including fundus examination, intravenous fluorescein angiogram, spectral-domain optical coherence tomography, and electroretinogram. Six patients have a 30-year follow-up. Histopathology examination was performed on eyes of the eldest patient. Whole exome sequencing was done in four affected subjects. RESULTS: Findings include a decreased visual acuity, abnormal cellophane-like sheen of the vitreoretinal interface, a "plush" nerve fiber layer, and characteristic macular changes. Electroretinogram showed a selective b-wave diminution. Intravenous fluorescein angiogram presented perifoveal hyperfluorescence and capillary leakage. Spectral-domain optical coherence tomography revealed cavitations involving inner and later outer retinal layers with later disorganization. Histopathologic findings included Müller cell abnormalities with cystic disruption of inner retinal layers, pseudoexfoliation in anterior segment, and amyloidosis of extraocular vessels. Pedigree analysis suggests an autosomal dominant inheritance with late onset. DNA analysis demonstrated a previously undescribed heterozygous missense p.Glu109Val mutation in transthyretin. CONCLUSION: To the best of our knowledge, this is the first family reported with this disorder. Our data support the hypothesis that autosomal dominant Müller cell dystrophy is a distinct retinal dystrophy affecting Müller cells. Mutations in transthyretin gene may manifest as a predominantly retinal disorder.

Safety of intravitreal quinupristin/dalfopristin in an animal model.

AIM: To determine whether different intravitreal doses of quinupristin/dalfopristin lead to electroretinographic or histological changes in the rabbit retina over one month period after injection. METHODS: Eighteen New Zealand white rabbits were divided into three treatment groups (groups 1 to 3) and different intravitreal doses of quinupristin/dalfopristin were tested in each group. The right eye was injected with the drug and the left eye received intravitreal injection of 5% dextrose water and served as control eye. The doses delivered to each group were 0.1 mg/0.1 mL, 1 mg/0.1 mL and 10 mg/0.1 mL. Simultaneous, bilateral, dark-adapted electroretinography and clinical images of both eyes were obtained in all groups before injection (baseline) and after 7, 14, 21 and 28d, followed by enucleation for histological examination. RESULTS: Subjects in the group 1 showed no signs of toxicity in the electroretinogram when compared with groups 2 and 3 (Kruskall-Wallis test, P=0.000). By day 7, no electrical response to light stimuli was recorded in the treated eyes in groups 2 and 3, consistent with severe damage due to retinal toxicity. Light microscopy revealed no significant histopathological changes in the group 1, while rabbits in groups 2 and 3 had signs of granulomatous inflammation in most cases. CONCLUSION: Intravitreal 0.1 mg/0.1 mL doses of quinupristin/dalfopristin do not lead to electroretinographic or histological signs of retinal toxicity compared with 1 mg/0.1 mL and 10 mg/0.1 mL in this rabbit model.

Paracentral cone dystrophy with tapetal-like sheen and mizuo phenomenon examined with different imaging techniques.

PURPOSE: To present a case report of a patient diagnosed with cone dystrophy, with an uncommon presentation of paracentral involvement, tapetallike sheen, and Mizuo phenomenon. METHODS: The patient underwent complete ophthalmic examination, repeated electroretinograms, fluorescein angiography, spectral-domain optical coherence tomography, autofluorescence, and different techniques for fundus photographs (color, infrared, red free). PATIENT: Twenty-year-old male patient who manifested slight photofobia but was otherwise asymptomatic. RESULTS: The patient had 20/20 vision in both eyes. Upon indirect ophthalmoscopy, the retina presented a metalliclike sheen. Sequential electroretinograms and multifocal electroretinogram demonstrated a decreasing photopic response, with paracentral involvement. Autofluorescence and spectral-domain optical coherence tomography allowed a better visualization of the atrophic parafoveal cones. Red-free photographs help document the tapetallike sheen and Mizuo phenomenon after 3-hour dark adaptation. CONCLUSION: The final diagnosis of cone dystrophy, paracentral, with tapetallike sheen was established. Spectral-domain optical coherence tomography and red-free photographs will help better understand the pathophysiology and clinical manifestations of this uncommon disease.

Multifocal electrophysiologic findings after intravitreal bevacizumab (avastin) treatment.

PURPOSE: To determine the short-term safety of intravitreal bevacizumab by multifocal electroretinography testing. METHODS: Thirty-one eyes with choroidal neovascularization, proliferative diabetic retinopathy, and retinal vein occlusion received intravitreal bevacizumab (2.5 mg/0.1 mL). All patients underwent best-corrected visual acuity measurement, retinal fluorescein angiography, optical coherence tomography, and multifocal electroretinography at baseline and 1 month after the treatment. RESULTS: Subjects undergoing multifocal electroretinography testing had no statistically significant changes in electrophysiologic responses 1 month after the intravitreal injection of bevacizumab. CONCLUSION: Multifocal electrophysiologic testing did not demonstrate any short-term cone photoreceptor toxicity after intravitreal bevacizumab.

Tractional retinal detachment after intravitreal injection of bevacizumab in proliferative diabetic retinopathy.

PURPOSE: To assess the short-term complications of a single dose of intravitreal bevacizumab in patients with proliferative diabetic retinopathy (PDR). METHODS: Retrospective review of 343 patients with PDR who were treated with intravitreal injection of bevacizumab (2.5 mg/0.1 mL). RESULTS: Five patients (1.45%) presented tractional retinal detachment 1 to 6 weeks (mean 3 weeks) after intravitreal injection. All cases underwent pars plana vitrectomy, removal of all epiretinal fibrovascular membranes, further endolaser panretinal photocoagulation, and silicone tamponade. CONCLUSION: Tractional retinal detachment may occur in a short time post intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy with extensive areas of ischemia and fibrovascular proliferations, and may require prompt vitreoretinal surgery.

Vitrectomy with complete posterior hyaloid removal for ischemic central retinal vein occlusion: series of cases.

BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder with potentially complications: (1) persistent macular edema and (2) neovascular glaucoma. No safe treatment exists that promotes the return of lost vision. Eyes with CRVO may be predisposed to vitreous degeneration. It has been suggested that if the vitreous remains attached to the macula owing to a firm vitreomacular adhesion, the resultant vitreous traction can cause inflammation with retinal capillary dilation, leakage and subsequent edema6. The roll of vitrectomy in ischemic CRVO surgical procedures has not been evaluated. CASE PRESENTATION: This is a non comparative, prospective, longitudinal, experimental and descriptive series of cases. Ten eyes with ischemic CRVO. Vitrectomy with complete posterior hyaloid removal was performed. VA, rubeosis, intraocular pressure (IOP), and macular edema were evaluated clinically. Multifocal ERG (m-ERG), fluorescein angiography (FAG) and optic coherence tomography (OCT) were performed. Follow-up was at least 6 months. Moderate improvement of visual acuity was observed in 60% eyes and stabilized in 40%. IOP changed from 15.7 +/- 3.05 mmHg to 14.9 +/- 2.69 mmHg post-operative and macular edema from 976 +/- 196 microm to 640 +/- 191 microm to six month. The P1 wave amplitude changed from 25.46 +/- 12.4 mV to 20.54 +/- 11.2 mV. CONCLUSION: A solo PPV with posterior hyaloid removal may help to improve anatomic and functional retina conditions in some cases. These results should be considered when analyzing other surgical maneuvers.