Peripheral-to-central ratio of Guttae: validity and reliability of an objective method to characterize severity of Fuchs endothelial corneal dystrophy.

PURPOSE: Common methods of measuring severity of Fuchs endothelial corneal dystrophy (FECD) are limited in objectivity, reliability, or start with a variable baseline that prevents distinguishing healthy from affected eyes. The aim of this study was to describe a method of grading FECD that overcomes these limitations. METHODS: Fifteen patients with Fuchs endothelial corneal dystrophy were included in the study. Guttae were imaged with a slit lamp beam 8 mm tall; the bottom 4 mm half of each image was divided into two equally-sized sections. Guttae were counted by four independent graders blinded to disease severity scores. The peripheral:central guttae ratio was compared to modified Krachmer clinical severity scores. The peripheral:central guttae ratio was compared between mild (severity 0.5-3) versus moderate-to-severe (severity 4-5) disease. Receiver operating characteristics defined optimal ratio cutoffs for mild versus moderate-to-severe disease. RESULTS: Increased peripheral guttae and peripheral:central guttae ratio correlated with Krachmer severity (p = 0.021 and p = 0.009, respectively). The difference between mild and moderate-to-severe cases for the peripheral:central guttae ratio was significant (p < 0.001). Inter-rater reliability of total guttae count was high (coefficient = 0.82, p < 0.001). A peripheral:central guttae ratio of 0.16 was the ideal cut-off point (area under the curve = 0.79, sensitivity = 0.78, and specificity = 0.80). CONCLUSION: In this pilot study, the peripheral:central ratio of guttae correlates with subjective clinical severity of Fuchs dystrophy. It starts at a common baseline, has good inter-rater reliability, does not require dilation, and can be conducted with a smartphone and slit-lamp.

IL-1ß/TNF-α/IL-6 inflammatory cytokines promote STAT1-dependent induction of CH25H in Zika virus-infected human macrophages.

Zika virus (ZIKV)3 is an enveloped, single-stranded, positive-sense RNA virus of the Flaviviridae family that has emerged as a public health threat because of its global transmission and link to microcephaly. Currently there is no vaccine for this virus. Conversion of cholesterol to 25-hydroxycholesterol by cholesterol 25-hydroxylase (CH25H) has been shown to have broad antiviral properties. However, the molecular basis of induction of CH25H in humans is not known. Elucidation of signaling and transcriptional events for induction of CH25H expression is critical for designing therapeutic antiviral agents. In this study, we show that CH25H is induced by ZIKV infection or Toll-like receptor stimulation. Interestingly, CH25H is induced by pro-inflammatory cytokines, including IL-1ß, tumor necrosis factor α, and IL-6, and this induction depends on the STAT1 transcription factor. Additionally, we observed that cAMP-dependent transcription factor (ATF3) weakly binds to the CH25H promoter, suggesting cooperation with STAT1. However, ZIKV-induced CH25H was independent of type I interferon. These findings provide important information for understanding how the Zika virus induces innate inflammatory responses and promotes the expression of anti-viral CH25H protein.

Validating the accuracy of an activity monitor in a visually impaired older population.

PURPOSE: Activity monitors have been used to objectively measure physical activity and its association with visual impairment in older adults. However, there is limited understanding of the accuracy of activity monitors in people with low vision. This study investigated the accuracy of an activity monitor compared with manual step counting in a low vision population and sought to find the most accurate placement location for the device. METHODS: We recruited 32 individuals aged 50 years and older with low vision. ActiGraph activity monitors were secured bilaterally on the wrists, ankles, and hips of each participant, who then walked a flat, linear course in their home at a comfortable pace for 4 min, using any necessary assistive device such as a long cane, support cane, or guide dog. Steps were counted using a hand-held tally counter. ActiGraph-measured step data from the 4-min period were downloaded using the standard and low frequency filters at 1 epoch s-1 through ActiLife. RESULTS: Of the 32 participants, 20 (63%) were female, median visual acuity was 1.48 logMAR (6/180 Snellen), average age was 73 (standard deviation, S.D., 9) years, average body mass index was 28.9 (S.D. 7.0) kg m-2 , and 47% of participants used an assistive device. Average distance for the test course was 10.9 (S.D. 3.4) m and participants completed an average of 368 (S.D. 68) steps during the 4 min. The number of steps recorded by the two, bilaterally-worn devices at each location were averaged. Ankle, hip, and wrist activity monitors detected 85% (interquartile range, IQR 76-94%), 56% (IQR 39-85%), and 56% (IQR 43-69%), respectively, of directly-observed steps when using the standard ActiGraph filter. Detected steps more closely matched directly observed steps for all placement sites when the low-frequency ActiGraph filter was applied: 101% (IQR 99-104%) at the ankle, 94% (IQR 85-101%) at the hip, and 83% (IQR 72-94%) at the wrist. Bland-Altman plots showed greater levels of agreement between ActiGraph-recorded and directly-observed steps at faster walking speeds. CONCLUSIONS: Our results demonstrate that the most accurate location of activity monitor placement is the ankle and that when using the low-frequency filter the level of agreement becomes more acceptable on the wrist and hip, in this population. Use of the low activity filter can help minimise inaccurate calculation of steps in people with low vision, particularly those who walk slowly.

Outcomes of a Modified Trabeculectomy Closure Technique.

PRECIS: A modified closure for trabeculectomy in which the conjunctiva is incised posterior to the limbus and reapproximated using 2 nylon sutures, provided similar surgical outcomes to the standard trabeculectomy closure technique. PURPOSE: To examine the surgical outcomes of a modified trabeculectomy closure technique in which the conjunctiva is incised posterior to the limbus and reapproximated using 2 sutures, burying the posterior conjunctiva under an anterior lip of conjunctiva. MATERIALS AND METHODS: This retrospective review included 73 eyes that underwent trabeculectomies between 2015 and 2017 at Johns Hopkins Hospital by a single surgeon. We analyzed traditional closures used from January 2015 to May 2016, and modified closures used from July 2016 to March 2017. The main outcome measures were a reduction in intraocular pressure at 3, 6, and 12 months, reduction in the number of medications at 12 months, and total number of postoperative complications. RESULTS: There was no difference in reduction of intraocular pressure at 3 months (9.9±8.2 vs. 10.5±8.7 mm Hg), 6 months (10.8±9.6 vs. 10.6±8.3 mm Hg), or 12 months (12.2±8.9 vs. 10.0±9.3 mm Hg) in the standard (n=44) and modified groups (n=29), respectively. There was a similar reduction in the use of glaucoma medications in the standard group (1.2±1.5 vs. 1.0±1.1) compared with the modified group and no difference in the number of postoperative complications (25.0% vs. 17.2%, respectively) (P>0.05 for all). CONCLUSIONS: The modified closure provided similar results to the standard closure for trabeculectomy. Further studies are needed to determine whether the 2 techniques differ in surgical outcomes over a longer follow-up or other surgical parameters (eg, ease, surgical time, learning curve).