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4.
Autophagy ; 12(10): 1876-1885, 2016 10 02.
Article in English | MEDLINE | ID: mdl-27463423

ABSTRACT

Autophagy is critical for maintaining cellular homeostasis. Organs such as the eye and brain are immunologically privileged. Here, we demonstrate that autophagy is essential for maintaining ocular immune privilege. Deletion of multiple autophagy genes in macrophages leads to an inflammation-mediated eye disease called uveitis that can cause blindness. Loss of autophagy activates inflammasome-mediated IL1B secretion that increases disease severity. Inhibition of caspase activity by gene deletion or pharmacological means completely reverses the disease phenotype. Of interest, experimental uveitis was also increased in a model of Crohn disease, a systemic autoimmune disease in which patients often develop uveitis, offering a potential mechanistic link between macrophage autophagy and systemic disease. These findings directly implicate the homeostatic process of autophagy in blinding eye disease and identify novel pathways for therapeutic intervention in uveitis.


Subject(s)
Autophagy , Eye Diseases/pathology , Inflammation/pathology , Macrophages/pathology , Animals , Autophagy/genetics , Autophagy-Related Protein 5/metabolism , Autophagy-Related Proteins/genetics , Cytokines/genetics , Cytokines/metabolism , Gene Deletion , Gene Expression Regulation , Humans , Inflammasomes/metabolism , Inflammation/genetics , Interleukin-1beta/metabolism , Macrophages/ultrastructure , Mice, Knockout , Polymorphism, Single Nucleotide/genetics , Uveitis/complications , Uveitis/genetics , Uveitis/pathology
5.
J Cataract Refract Surg ; 35(6): 1082-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19465295

ABSTRACT

PURPOSE: To report the incidence of and factors associated with rainbow glare after laser in situ keratomileusis (LASIK) flap creation with a 60 kHz femtosecond laser. SETTING: Department of Refractive Surgery, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, USA. METHODS: Consecutive patients having LASIK by the same surgeon were questioned during postoperative examinations or by telephone about postoperative rainbow glare (radiating colors around a white light at night). Femtosecond laser (IntraLase) settings included pulse frequency 60 kHz, flap thickness 90 to 110 mum, and spot/line separation 8 mum. Raster energy was 0.8 microJ (75% of eyes) and 1.0 to 1.1 microJ (25%). Excimer laser ablation was performed with the LADAR 4000 or 6000 platform using custom or conventional treatments. RESULTS: Of 260 consecutive patients, 256 (98.5%) were successfully contacted. Fifteen patients (28 eyes) reported postoperative rainbow glare (5.8%), described as 4 to 12 bands of color around a white light, with 6 bands most common. The symptom did not correlate with refractive error, age, or sex but was more frequent at 1.0 microJ or 1.1 microJ raster energy (11.6%) than at 0.8 microJ (4.1%). The incidence followed a bimodal distribution, with the first grouping due to inadequate alignment and higher energy just after laser installation and the second just before a later maintenance service call. CONCLUSION: Rainbow glare is a mild optical side effect of femtosecond LASIK. In this study, higher raster energy levels and length of time between service calls were associated with the occurrence of rainbow glare.


Subject(s)
Glare , Keratomileusis, Laser In Situ/adverse effects , Lasers, Excimer/adverse effects , Surgical Flaps , Vision Disorders/etiology , Corneal Stroma/surgery , Humans , Incidence , Myopia/surgery , Surveys and Questionnaires , Vision Disorders/epidemiology
6.
J Refract Surg ; 24(9): 953-6, 2008 11.
Article in English | MEDLINE | ID: mdl-19044238

ABSTRACT

PURPOSE: To describe a series of myopic patients in whom a LASIK flap was created with the IntraLase femtosecond laser. The LADARVision (Alcon Laboratories Inc) tracking system failed and resulted in postponement of surgery. METHODS: Five myopic Asian patients with darkly pigmented irides underwent bilateral superior hinge flap creation with three different femtosecond laser (IntraLase Corp) pulse frequencies: 15, 30, and 60 kHz. Mean patient age, preoperative best spectacle-corrected visual acuity (BSCVA), and spherical equivalent refraction were 33 years, 20/20, and -6.25 diopters (D), respectively. Despite uncomplicated flap-lift and adequate pharmacologic dilated pupil diameter >7 mm, difficulty was experienced with LADARVision eye tracking in 9 of 10 eyes. Intraoperative manipulations (fluid application, levitation of the laser bed, and tracking through a repositioned flap) were attempted to facilitate eye tracking at the time of femtosecond laser flap creation, but without success. RESULTS: The flap was repositioned, and patients were asked to return 1 to 5 days later, at which time the flap was relifted, eye tracking was successfully achieved, and the surgery was completed. Mean postoperative uncorrected visual acuity was 20/18 and no eyes lost any lines of BSCVA at 1 year. CONCLUSIONS: Irregularities of the IntraLASIK stromal bed surface induce forward light scatter, and dark ocular pigmentation further reduces retinal reflectance, leading to tracking failure with the Alcon LADARVision platform. Delaying the surgery by 1 to 5 days may aid in reducing the light scatter, so that eye tracking can be achieved.


Subject(s)
Corneal Stroma/surgery , Eye Movements , Intraoperative Complications , Keratomileusis, Laser In Situ , Lasers, Excimer/therapeutic use , Surgical Flaps , Adult , Eye Color , Female , Humans , Male , Myopia/surgery , Visual Acuity
7.
Cornea ; 27(9): 1074-6, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18812776

ABSTRACT

PURPOSE: To describe the history, clinical presentation, and successful medical management of a case of multidrug-resistant Flavobacterium indologenes keratitis. METHODS: An 83-year-old pseudophakic female presented with a 2-day history of decreased visual acuity, light sensitivity and dull ocular pain in her right eye. Two weeks before presentation, the patient had been treated for a red eye with combination topical loteprednol etabonate (0.5%) and tobramycin (0.3%) eye drops. Corneal scrappings were performed by the referring ophthalmologist, and hourly administration of gatifloxacin 0.3% eye drops was started. Evaluation consisted of slit lamp examination, organism identification, and antibiotic sensitivity testing. RESULTS: Examination of the right eye revealed a central 5-mm X 2-mm anterior stromal infiltrate with an overlying epithelial defect. Gatifloxacin 0.3% eye drops were stopped, and hourly topical fortified vancomycin (50 mg/mL) and ceftazidime (50 mg/mL) eye drops were instituted. Oxidase-positive gram-negative bacilli were identified in the thioglycollate broth on day 3, and therefore, vancomycin was discontinued and hourly ciprofloxacin 0.3% eye drops were added to the regimen. The cultures ultimately grew F. indologenes, which was highly resistant to all antibiotics tested except for trimethoprim-sulfamethoxazole. Accordingly, ciprofloxacin 0.3% and ceftazidime were discontinued. The patient was started on hourly topical trimethoprim (16 mg/mL)/sulfamethoxazole (80 mg/mL) eye drops, resulting in clinical control of the infection over a period of 1 month. CONCLUSIONS: Flavobacterium indologenes keratitis can be resistant to treatment with many medications, and antibiotic susceptibility profile testing in these cases may provide crucial information to help eradicate the infection.


Subject(s)
Anti-Infective Agents/therapeutic use , Drug Resistance, Multiple, Bacterial , Flavobacteriaceae Infections/drug therapy , Flavobacterium/physiology , Keratitis/microbiology , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Aged, 80 and over , Female , Humans , Keratitis/pathology , Keratitis/physiopathology , Microbial Sensitivity Tests , Visual Acuity
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