Surgical Approach for Monoclonal Gammopathy of Undetermined Significance-Related Ocular Copper Deposition.

PURPOSE: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens. RESULTS: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye. CONCLUSIONS: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition.

CMOS Detector Staggered Array Module for Sub-Terahertz Imaging on Conveyor Belt System.

A complementary metal-oxide-semiconductor (CMOS) detector array is proposed to improve the sub-terahertz imaging resolution for objects in the conveyor belt system. The image resolution is limited to the implemented configuration, such as the wide spacing in the detector array, the high conveyor belt speed, and the slow response of the signal conditioning block. The proposed array can improve the image resolution in the direction perpendicular to the movement of the belt, which is determined by the size and interval of the detector pixel, by configuring the array into two replaceable columns located at the misaligned horizontal positions. Replaceable detector unit pixels are individually attached to the motherboard after measuring and evaluating the detection performance to construct the proposed array. The intensities of 32 detector pixels placed under the conveyor belt with a width of 160 mm were initially calibrated in every image, including the beam pattern of 0.2 THz signals generated from the gyrotron. The image resolution of the perpendicular direction obtained from the proposed array was measured to be approximately 5 mm at a conveyor belt speed of 16 mm/s, demonstrating a 200% improvement in resolution compared to the conventional linear array under the same conditions.

Concurrent-Mode CMOS Detector IC for Sub-Terahertz Imaging System.

A CMOS detector with a concurrent mode for high-quality images in the sub-terahertz region has been proposed. The detector improves output-signal coupling characteristics at the output node. A cross-coupling capacitor is added to isolate the DC bias between the drain and gate. The detector is designed to combine a 180° phase shift based on common source operation and an in-phase output signal based on the drain input. The circuit layout and phase shift occurring in the cross-coupled capacitor during phase coupling are verified using an EM simulation. The detector is fabricated using the TSMC 0.25-µm mixed-signal 1-poly 5-metal layer CMOS process, where the size, including the pad, is 1.13 mm × 0.74 mm. The detector IC comprises a folded dipole antenna, the proposed detector, a preamplifier, and a voltage buffer. Measurement results using a 200-GHz gyrotron source demonstrate that the proposed detector voltage responsivity is 14.13 MV/W with a noise-equivalent power of 34.42 pW/√Hz. The high detection performance helps resolve the 2-mm line width. The proposed detector exhibits a signal-to-noise ratio of 49 dB with regard to the THz imaging performance, which is 9 dB higher than that of the previous CMOS detector core circuits with gate-drain capacitors.

Case series: Delayed diagnoses of Acanthamoeba keratitis.

PURPOSE: To describe two cases of Acanthamoeba keratitis in contact lens wearers misdiagnosed as Herpes simplex keratitis. OBSERVATIONS: Case 1 is a 54-year-old male that was misdiagnosed with Herpes simplex keratitis who developed advanced Acanthamoeba keratitis. His treatment course was complex and involved both medical therapy and surgical intervention with poor resolution. Case 2 is an 18-year-old male who was also initially misdiagnosed and treated for Herpes simplex keratitis, but ultimately treated with polyhexamethylene biguanide and chlorhexidine with complete resolution. CONCLUSIONS AND IMPORTANCE: The clinical presentation of Acanthamoeba keratitis may closely resemble other causes of keratitis and continues to be misdiagnosed, leading to delayed diagnosis and treatment. However, given the significant morbidity and challenging treatment course for Acanthamoeba keratitis, it is important for clinicians to maintain a high suspicion for Acanthamoeba and to consider obtaining cultures in contact lens wearers with atypical keratitis prior to making a diagnosis of Herpes simplex keratitis.

The Association between Frailty and Uncorrected Refractive Error in Older Adults.

Purpose: Uncorrected refractive error (URE) is the leading cause of impaired vision in older adults and has been associated with adverse health outcomes. Here, we investigate the association between URE and frailty in older adults.Methods: This is a cross-sectional analysis of National Health and Nutrition Examination Survey (NHANES) participants ≥60 years (1999-2006 cycles). URE was defined as visual acuity worse than 6/12 that can be improved with correction, and prefrailty and frailty were defined as meeting 1-2 and ≥3 of 4 components of a modified physical frailty phenotype. The 5-item phenotype (including slowness) was analyzed in a subset of participants with available data. Propensity score adjustment was used to address the imbalance of potential confounders (including age) between URE groups.Results: In this sample (n = 5,265), 6% of participants had URE (n = 373). In fully adjusted propensity score-based models, individuals with URE were more likely to be prefrail (OR = 1.4; 95% CI: 1.0-2.0) and frail (OR = 3.2; 95% CI: 1.3-7.4) than those without URE using the 4-item phenotype. For the 2,486 participants with 5-item phenotype data, individuals with URE were more likely to be frail (OR = 3.0; 95% CI: 1.2-7.5); however, the association with prefrailty was not statistically significant (OR = 1.8; 95% CI: 0.9-3.6).Conclusion: In this population-based sample, older adults with URE were more likely to be frail than those without URE, even after rigorous control for confounders, including age.

Association Between Microvascular Retinal Signs and Age-Related Hearing Loss in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS).

Importance: Given that age-related hearing loss is highly prevalent and treatable, understanding its causes may have implications for disease prevention. Objective: To investigate whether microvascular retinal signs are associated with age-related hearing loss attributable to a hypothesized underlying shared pathologic entity involving microvascular disease. Design, Setting, and Participants: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) is a community-based prospective cohort study of 15 792 men and women aged 45 to 64 years at baseline. The ARIC-NCS participants returned for a fifth clinic visit in 2011-2013 and a sixth clinic visit in 2016-2017. Participants were recruited from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). Participants included a subset of the ARIC-NCS cohort with complete covariate data who underwent retinal fundus photography at visit 5 (2011-2013) and completed hearing assessment at visit 6 (2016-2017) (N = 1458). Overall, 453 participants had diabetes; of those, 68 had retinopathy. Of 1005 participants without diabetes, 42 had retinopathy. Exposures: Microvascular retinal signs included retinopathy, arteriovenous (AV) nicking, and generalized arteriolar narrowing measured using the central retinal arteriolar equivalent (CRAE). Main Outcomes and Measures: Hearing was measured using the better-hearing ear pure-tone average (PTA) of air conduction speech thresholds (0.5, 1, 2, and 4 kHz). Multivariable-adjusted linear and ordered logistic regression was used to estimate the association between microvascular retinal signs and age-related hearing loss to describe the precision of the estimates and provide a plausible range for the true association. Results: After full adjustment among 1458 individuals in the analytic cohort (mean [SD] age, 76.1 [5.0] years [age range, 67-90 years]; 825 women [56.6%]; 285 black [19.5%]), the difference in PTA per dB hearing level in persons with and without retinopathy was 2.21 (95% CI, -0.22 to 4.63), suggesting that retinopathy is associated with poorer hearing, although the width of the 95% CI prevents definitive conclusions about the strength of the observed association. Restricting the analysis to participants without diabetes, the difference in PTA associated with retinopathy was even greater (4.14; 95% CI, 0.10-8.17 dB hearing level), but the large width of the 95% CI prevents definitive conclusions about the association. In analyses quantifying the mean differences in hearing thresholds at individual frequencies by retinopathy status, the estimates trended toward retinopathy being associated, contrary to expectation, with better high-frequency hearing. At 8 kHz, the estimated difference in hearing thresholds in persons with retinopathy vs those without was -4.24 (95% CI, -7.39 to -1.09). Conclusions and Relevance: In this population-based study, an association between the presence of microvascular retinal signs and hearing loss was observed, suggesting that retinopathy may have the potential to identify risk for hearing loss in persons without diabetes. The precision of these estimates is low; therefore, additional epidemiologic studies are needed to better define the degree of microvascular contributions to age-related hearing loss.

Near Vision Impairment and Frailty: Evidence of an Association.

PURPOSE: To examine associations between near vision impairment (NVI) and frailty. DESIGN: Cross-sectional study. METHODS: Setting: Nationally representative sample of noninstitutionalized United States civilians. STUDY POPULATION: Total of 2705 older adults aged ≥60 years from National Health and Nutrition Examination Survey (1999-2002). OBSERVATION: Presenting NVI (PNVI): near acuity worse than 20/40. Self-reported NVI (SNVI): self-reported difficulty with near vision tasks. MAIN OUTCOME MEASURE(S): Five-item physical frailty index; participants classified as frail (≥3 criteria) and prefrail (1 or 2 criteria). Propensity score-adjusted and probability-weighted multinomial multivariable logistic regression was used to examine associations of PNVI and SNVI with frailty. RESULTS: Of 2705 participants, 381 (10%), 160 (5%), and 106 (3%) had PNVI only, SNVI only, and PNVI+SNVI, respectively. In fully adjusted models, as compared to those without PNVI, participants with PNVI were more likely to be prefrail (odds ratio [OR] = 1.6; 95% confidence interval [CI] = 1.1, 2.3) and frail (OR = 2.5; 95% CI = 1.4, 4.3). As compared to those without SNVI, participants with SNVI were more likely to be prefrail (OR = 2.9; 95% CI = 1.8, 4.7) and frail (OR = 4.3; 95% CI = 2.2, 8.3). As compared to those without PNVI or SNVI, participants with PNVI+SNVI were more likely to be prefrail and frail (prefrail: OR = 4.0; 95% CI = 2.2, 7.2 and frail: OR = 4.5; 95% CI = 1.7,12.7). CONCLUSIONS: Older adults with PNVI and SNVI were more likely to be prefrail and frail than those without respective NVI, suggesting that NVI is associated with frailty.

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).

Prevalence of Retinal Signs and Association With Cognitive Status: The ARIC Neurocognitive Study.

OBJECTIVE: To determine the prevalence of retinal microvascular signs and associations between retinal signs and cognitive status. DESIGN: Cross-sectional analysis of visit 5 (2011-2013) of the Atherosclerosis Risk in Communities (ARIC) cohort. Data analysis took place November 30, 2017, to May 1, 2018. SETTING: Biracial population-based cohort from four US communities. PARTICIPANTS: A total of 2624 participants with a mean age of 76 years (SD = 5 years) (19% African American) with data on cognitive status and complete retinal examination. MEASUREMENTS: Retinal signs measured with fundus photography. Cognitive status: normal cognition, mild cognitive impairment (MCI)/dementia with a primary diagnosis of Alzheimer disease (AD) without cerebrovascular disease (CVD), and MCI/dementia with a primary or secondary diagnosis of CVD (irrespective of AD). RESULTS: Overall, 6% of the cohort had mild retinopathy and 2% had moderate/severe retinopathy. Of the cohort, 7% had microaneurysms, 6% had retinal hemorrhages, and 8% had arteriovenous (AV) nicking. There was a low prevalence of soft exudates (1%) and focal narrowing (1%). In weighted fully adjusted models, individuals with retinal hemorrhages had a two-fold higher odds of all-cause MCI/dementia (95% confidence interval [CI] = 1.3-3.0; P = .001) and a 2.5-fold higher odds (95% CI = 1.6-3.9; P < .001) of MCI/dementia with CVD compared to individuals with no retinal hemorrhages. Individuals with AV nicking had a 1.6-fold higher odds of MCI/dementia with CVD (95% CI = 1.0-2.4) compared to individuals with no AV nicking (P < .05). There were no associations between retinal signs and MCI/dementia without CVD. CONCLUSION: Our findings are confirmatory of recent research, and suggest that retinal microvascular signs may reflect microvascular pathology in the brain, potentially contributing to dementia and earlier MCI. The low prevalence of retinal signs and modest associations with cognitive status, however, limit the current clinical utility of these findings. Further work is needed to determine whether more sophisticated imaging may detect more subtle retinal signs with higher sensitivity to identify individuals at risk of dementia.

Memory and Confusion Complaints in Visually Impaired Older Adults: An Understudied Aspect of Well-Being.

Objective: To determine the prevalence of cognitive (memory or confusion) complaints in older adults with visual impairment (VI). Method: We assessed the relationship between VI (corrected visual acuity [VA] < 20/40) and self-reported confusion or problems with memory among participants aged 60 years to 85 years in the 1999-2006 cycles of National Health and Nutrition Examination Survey (n = 5,795). Prevalence estimates of cognitive complaints were calculated using Current Population Surveys. Results: Memory/confusion complaints were reported in 22% of the VI group and 11% of the no VI group (p < .001). In individuals aged ≥ 80 years, 30% of those with VI reported cognitive complaints, as compared with 19% with no VI (p = .003). In fully adjusted models, individuals with VI were more likely (OR = 1.3, p = .049) to report cognitive complaints as compared with those without VI. Conclusion: Subjective reports of memory or confusion are highly prevalent in older individuals with VI.

Greater Physical Activity Is Associated with Slower Visual Field Loss in Glaucoma.

PURPOSE: To determine the association between physical activity levels and the rate of visual field (VF) loss in glaucoma. DESIGN: Longitudinal, observational study. PARTICIPANTS: Older adults with suspect or manifest glaucoma. METHODS: Participants wore accelerometers for 1 week to define average steps per day, minutes of moderate-to-vigorous activity, and minutes of nonsedentary activity. All available VF measurements before and after physical activity assessment were retrospectively analyzed to measure rates of VF loss. MAIN OUTCOME MEASURES: Pointwise changes in VF sensitivity associated with physical activity measures. RESULTS: A total of 141 participants (mean age, 64.9±5.8 years) were enrolled. Eye mean deviation (MD) at the time of physical activity assessment was -6.6 decibels (dB), and average steps per day were 5613±3158. The unadjusted average rate of VF loss as measured by pointwise VF sensitivity was 0.36 dB/year (95% confidence interval, -0.37 to -0.35). In multivariable models, slower VF loss was observed for patients demonstrating more steps (+0.007 dB/year/1000 daily steps, P < 0.001), more moderate-to-vigorous activity (+0.003 dB/year/10 more minutes of moderate-to-vigorous activity per day, P < 0.001), and more nonsedentary activity (+0.007 dB/year/30 more minutes of nonsedentary time per day, P = 0.005). Factors associated with a faster rate of VF loss included older age, non-white race, glaucoma surgery, cataract surgery, and moderate baseline VF damage (-6 dB ≥ MD >-12 dB) as opposed to mild VF damage (MD >-6 dB). Similar associations between baseline accelerometer-measured physical activity and rates of VF loss were observed over other time periods (e.g., within 1, 3, and 5 years of activity assessment). CONCLUSIONS: Increased walking, greater time spent doing moderate-to-vigorous physical activity, and more time spent in nonsedentary activity were associated with slower rates of VF loss in a treated population of patients with glaucoma, with an additional 5000 daily steps or 2.6 hours of nonsedentary physical activity decreasing the average rate of VF loss by approximately 10%. Future prospective studies are needed to determine if physical activity can slow VF loss in glaucoma or if progressive VF loss results in activity restriction. If the former is confirmed, this would mark physical activity as a novel modifiable risk factor for preventing glaucoma damage.

The Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC) trial: Rationale and design of a multi-center, double-blind, placebo-controlled trial of high dose bolus administration of vitamin D3 during acute pulmonary exacerbation of cystic fibrosis.

Vitamin D deficiency is highly prevalent in children and adults with cystic fibrosis (CF). Recent studies have found an association between vitamin D status and risk of pulmonary exacerbations in children and adults with CF. The ongoing Vitamin D for enhancing the Immune System in Cystic fibrosis (DISC) study is a multi-center, double-blind, randomized, placebo-controlled trial that will test the hypothesis of whether high dose vitamin D given as a single oral bolus of 250,000 IU to adults with CF during a pulmonary exacerbation followed by a maintenance dose of vitamin D will improve time to next pulmonary exacerbation and re-hospitalization, improve survival and lung function compared to placebo and reduce the rates of pulmonary exacerbation,. Subjects will be randomized 1:1 at each clinical site to vitamin D or placebo within 72 hours of hospital admission for pulmonary exacerbation. Clinical follow-up visits will occur at 1, 2, 3, and 7 days, and 1, 3, 6 and 12 months after randomization. Blood and sputum will be collected and determination of clinical outcomes will be assessed at each visit. The primary endpoint will be the time to next pulmonary exacerbation requiring antibiotics, re-hospitalization or death. The secondary endpoints will include lung function assessed by forced expiratory volume in 1 second (FEV1), blood markers of inflammatory cytokines, anti-microbial peptide expression by peripheral blood mononuclear cells and circulating concentrations in blood. Other exploratory endpoints will examine the phenotype of neutrophils and monocyte/macrophages in sputum. Nutritional status will be assessed by 3 day food records and food frequency questionnaire.

High Dose Vitamin D Administration in Ventilated Intensive Care Unit Patients: A Pilot Double Blind Randomized Controlled Trial.

BACKGROUND: There is a high prevalence of vitamin D deficiency in the critically ill patient population. Several intensive care unit studies have demonstrated an association between vitamin D deficiency [25-hydroxyvitamin D (25(OH)D) < 20 ng/mL] and increased hospital length of stay (LOS), readmission rate, sepsis and mortality. MATERIAL AND METHODS: Pilot, double blind randomized control trial conducted on mechanically ventilated adult ICU patients. Subjects were administered either placebo, 50,000 IU vitamin D3 or 100,000 IU vitamin D3 daily for 5 consecutive days enterally (total vitamin D3 dose = 250,000 IU or 500,000 IU, respectively). The primary outcome was plasma 25(OH)D concentration 7 days after oral administration of study drug. Secondary outcomes were plasma levels of the antimicrobial peptide cathelicidin (LL37), hospital LOS, SOFA score, duration of mechanical ventilation, hospital mortality, mortality at 12 weeks, and hospital acquired infection. RESULTS: A total of 31 subjects were enrolled with 13 (43%) being vitamin D deficient at entry (25(OH)D levels < 20 ng/mL). The 250,000 IU and 500,000 IU vitamin D3 regimens each resulted in a significant increase in mean plasma 25(OH)D concentrations from baseline to day 7; values rose to 45.7±19.6 ng/mL and 55.2 ± 14.4 ng/mL, respectively, compared to essentially no change in the placebo group (21±11.2 ng/mL), p<0.001. There was a significant decrease in hospital length of stay over time in the 250,000 IU and the 500,000 IU vitamin D3 group, compared to the placebo group (25 ± 14 and 18 ± 11 days compared to 36 ± 19 days, respectively; p=0.03). There was no statically significant change in plasma LL-37 concentrations or other clinical outcomes by group over time. CONCLUSIONS: In this pilot study, high-dose vitamin D3 safely increased plasma 25(OH)D concentrations into the sufficient range and was associated with decreased hospital length of stay without altering other clinical outcomes. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01372995).

Free 25-Hydroxyvitamin D Concentrations in Cystic Fibrosis.

BACKGROUND: Vitamin D deficiency is common in cystic fibrosis (CF), but there is no previous data on free 25-hydroxyvitamin D (25[OH]D) in CF or in relation to healthy individuals. METHODS: We assessed total serum 25(OH)D concentration by chemiluminescence and serum free 25(OH)D concentration by both direct measurement (ELISA) and calculation, using serum albumin and vitamin D binding protein (VDBP) levels in 80 subjects (28 healthy adults, 25 clinically stable adults and children with CF and 27 adults experiencing a CF exacerbation). RESULTS: Serum albumin and VDBP concentrations were lower in CF compared with healthy controls. Total serum 25(OH)D concentrations were positively correlated with both calculated and measured free 25(OH)D (P < 0.001 for both). Calculated and directly measured serum free 25(OH)D levels were positively correlated (P < 0.001). CONCLUSIONS: Serum levels of directly measured free 25(OH)D positively correlated with total 25(OH)D, suggesting that achieving sufficient total serum 25(OH)D may result in adequate free 25(OH)D levels in CF.

Changes in Mineral Micronutrient Status During and After Pulmonary Exacerbation in Adults With Cystic Fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) may be at risk for micronutrient depletion, particularly during periods of illness and infection. The purpose of this study was to investigate serum micronutrient status over time in adults with CF initially hospitalized with a pulmonary exacerbation. MATERIALS AND METHODS: This was an ancillary study of a multicenter trial investigating the role of high-dose vitamin D supplementation in 24 adults with CF (mean age, 29.6 ± 7.3 years). We measured serum concentrations of copper (Cu), iron (Fe), calcium (Ca), magnesium (Mg), potassium (K), and sulfur (S) in subjects at the beginning of a pulmonary exacerbation and again at 3 months. RESULTS: Serum concentrations of Cu, Fe, and Ca were significantly lower at baseline compared with 3 months following the pulmonary exacerbation (Cu: baseline, 1.5 ± 0.6 vs 3 months, 1.6 ± 0.6 µg/mL, P = .027; Fe: 0.8 ± 0.3 vs 1.3 ± 1.1 µg/mL, P = .026; Ca: 9.7 ± 0.8 vs 10.8 ± 2.0 mg/dL, P = .024). Serum concentrations of K, Mg, and S did not change over time (K: baseline, 4.9 ± 0.3 vs 3 months, 5.1 ± 0.5 mEq/L; Mg: 1.8 ± 0.2 vs 2.0 ± 0.3 mg/dL; S: 1288.6 ± 343 vs 1309.9 ± 290 µg/mL; P > .05 for all). CONCLUSION: Serum concentrations of Cu, Fe, and Ca increased significantly several months following recovery from acute pulmonary exacerbation in adults with CF. This may reflect decreased inflammation, improved food intake, and/or increased absorption following recovery.