Eye Disease Prevalence and VF-14 Validation Among Patients Experiencing Homelessness and Presenting for Ophthalmic Examination in Baltimore, Maryland.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic is projected to drive 1.5 million Americans toward homelessness, adding to the 3.5 million currently affected. Homelessness poses both socioeconomic and public health challenges because housing status is a social determinant of health. Given ophthalmic health's importance in daily functioning, we characterized ophthalmic disease and vision-related quality of life (VRQOL) among a population experiencing homelessness in Baltimore, Maryland. Methods: Questionnaires, including a Visual Function Index-14 (VF-14) for measuring VRQOL, were administered among patients seeking eye examinations at Health Care for the Homeless (HCH) from October 2018 to March 2020. Results: One hundred sixty-two participants were enrolled in this study. The average age was 53 years. Participants' most common vision concerns were blurry vision (70%) and desire for glasses (52%). Best corrected visual acuity (BCVA) measurements revealed significant vision loss (18%, P < 0.001). Physicians mostly diagnosed refractive error (77%), cataracts (36%), glaucoma/glaucoma suspect (25%), and dry eye (24%). Nearly half were referred to additional ophthalmic care (46%). VRQOL trends reflected functional vision categories (P = 0.042 and P = 0.021). The 1:1 VRQOL and BCVA comparison showed correlation (rho = -0.3, P < 0.001). Cronbach's alpha demonstrated VF-14 reliability (alpha = 0.92). Conclusions: We find high ophthalmic disease prevalence within a population experiencing homelessness. Comparison to studies worldwide reveals healthcare disparities despite healthcare system differences, suggesting a need for more targeted solutions. VF-14 is valid and reliable in assessing those experiencing homelessness. Intragroup VRQOL comparisons may reveal subgroup needs. It is imperative that future studies continue monitoring those experiencing homelessness. Translational Relevance: Validation of VF-14 will allow future studies to utilize this patient-oriented metric within populations experiencing homelessness.

Oral minocycline for the treatment of retinitis pigmentosa-associated cystoid macular edema: results of a phase I/II clinical trial.

PURPOSE: The etiology of retinitis pigmentosa (RP)-associated cystoid macular edema (CME) has been related to retinal neuroinflammation and microglial activation. Minocycline, a drug FDA-approved for anti-microbial indications, also inhibits microglial activation and expression of inflammatory mediators. This study investigates the safety and efficacy of oral minocycline as primary treatment for RP-associated CME. METHODS: A single-center, prospective, open-label phase I/II clinical trial enrolled five participants with RP-associated CME. Participants had lead-in assessments prior to the initiation of oral minocycline 100 mg twice daily for 12 months. Main outcome variables included changes in best-corrected visual acuity (BCVA) and retinal central subfield thickness (CST) measured using spectral domain optical coherence tomography relative to mean of pre-treatment measurements. RESULTS: The study drug was well tolerated and not associated with any severe adverse events. No significant changes in mean BCVA from study baseline were noted in either the study eye (+ 0.7 ± 4.1 letters at 6 months, - 1.1 ± 1.7 letters at 12 months) or the qualifying fellow eye (- 0.3 ± 3.4 letters at 6 months, - 0.3 ± 4.6 letters at 12 months) (p > 0.05 for all comparisons). Mean percentage changes in CST from baseline however decreased progressively with treatment (decreases at 6 and 12 months: study eyes 3.9 and 9.8%; qualifying fellow eyes 1.4 and 7.7%). Considering all eyes (n = 10), mean percentage CST decrease at 6 and 12 months was 2.7 ± 9.5% (p = 0.39) and 8.7 ± 9.5% (p = 0.02) respectively. CONCLUSION: Oral minocycline administration over 12 months was associated with no significant changes in mean BCVA and a small but progressive decrease in mean CST. TRIAL REGISTRATION: NCT02140164 (05/2014).

LONGITUDINAL CHANGES IN EYES WITH HYDROXYCHLOROQUINE RETINAL TOXICITY.

PURPOSE: To characterize functional and structural changes in hydroxychloroquine (HCQ) retinal toxicity after drug cessation. METHODS: Twenty-two patients (91% female; mean age 58.7 ± 11.4 years; mean duration of HCQ treatment 161.1 ± 90 months; mean dose 5.9 ± 1.9 mg/kg) with detected HCQ retinopathy were monitored for 6 months to 82 months after HCQ cessation with multimodal imaging including spectral domain optical coherence tomography and fundus autofluorescence imaging at 488 nm (standard) and 787 nm (near-infrared autofluorescence). Tests of visual function including visual acuity, Humphrey visual field testing, and multifocal electroretinography (mfERG) were performed. Study eyes were categorized into four separate severity stages by qualitative grading of spectral domain optical coherence tomography macular scans taken at the time of HCQ cessation. Changes in outcome measures between drug cessation and last follow-up visit were computed and compared between eyes of different severity stages. RESULTS: Study eyes (n = 44) were categorized based on optical coherence tomography criteria into: Stage 1 (subtle changes confined to parafoveal region; n = 14), Stage 2 (clear localized changes in parafovea; n = 17), Stage 3 (extensive parafoveal changes; n = 7), and Stage 4 (foveal involvement, n = 6). Visual acuity measurements across follow-up were stable in Stage 1 and Stage 2 eyes but decreased significantly in Stage 3 and 4 eyes. Humphrey visual field measures were also stable in stages 1 and 2 but deteriorated in Stage 3 eyes. mfERG testing demonstrated significant improvement in the R1/R2 ratio after HCQ cessation in Stage 1 eyes (mean change = -0.86 ± 0.79, P = 0.03) but did not change significantly in eyes of higher stages. Decreases in macular thickness in ≥1 of 9 Early Treatment Diabetic Retinopathy Study subfields on spectral domain optical coherence tomography were found in eyes of all stages, with Stage 2 eyes demonstrating thinning in most subfields (eight of nine subfields). In eyes with a measurable central foveal ellipsoid zone band island (9 of 17 Stage 2 eyes and 7 of 7 Stage 3 eyes), progressive decrease in the foveal ellipsoid zone band length was observed in 6 of 9 (67%) Stage 2 eyes and 6 of 7 (86%) Stage 3 eyes. Changes indicative of progressing retinopathy were detected in 17% of Stage 1 eyes, 46% of Stage 2 eyes, and 43% of Stage 3 eyes on standard fundus autofluorescence imaging, and in 17% of Stage 1 eyes, 38% of Stage 2 eyes, and 14% of Stage 3 eyes on near-infrared autofluorescence imaging. CONCLUSION: Eyes with detected HCQ retinopathy do not demonstrate general stability in retinal structure and function after HCQ cessation but instead demonstrate a range of changes during follow-up whose magnitudes correlate with retinopathy severity at the time of cessation. After cessation, eyes with only subtle and localized retinopathy were mostly stable and may show some functional improvement, whereas more severely affected eyes continued to progress. These findings provide evidence that early detection and prompt cessation in HCQ retinopathy may be needed to arrest retinopathy progression and to optimize long-term outcomes.

Longitudinal Study of Dark Adaptation as a Functional Outcome Measure for Age-Related Macular Degeneration.

PURPOSE: To investigate the natural history of dark adaptation (DA) function as measured by the change in rod intercept time (RIT) over 4 years and to correlate RIT change with age-related macular degeneration (AMD) severity. DESIGN: Longitudinal, single-center, observational study. PARTICIPANTS: A total of 77 participants aged ≥50 years with a range of AMD severities. METHODS: Participants each contributing a single study eye to the analysis were assigned into person-based AMD severity groups based on fundus characteristics (drusen, pigmentary changes, late AMD, and subretinal drusenoid deposits [SDDs]). The DA function was assessed in study eyes at baseline and 3, 6, 12, 18, 24, 36, and 48 months. Mean change in DA function over time was calculated using the slope of linear regression fits of longitudinal RIT data. Patient-reported responses on a Low Luminance Questionnaire (LLQ) were obtained at baseline and yearly. Nonparametric statistical testing was performed on all comparisons. MAIN OUTCOME MEASURE: The RIT, defined as the time taken after a photobleach for visual sensitivity to recover detection of a 5×10-3 cd/m2 stimulus (a decrease of 3 log units), was monitored in study eyes over 4 years, and the mean rate of change was computed. RESULTS: Longitudinal analysis of 65 study eyes followed on the standard testing protocol (mean age, 71±9.3 years; 49% were female) revealed that higher rates of RIT prolongation were correlated with AMD severity group assignment at baseline (P = 0.026) and with severity group assignments at year 4 (P = 0.0011). Study eyes that developed SDD during follow-up demonstrated higher rates of RIT prolongation relative to those that did not (P < 0.0001). Overall, higher rates of RIT prolongation were significantly correlated with greater 4-year decreases in LLQ scores (total mean score, P = 0.0032). CONCLUSIONS: Longitudinal decline in DA function, which correlated with patient-reported functional deficits, was accelerated in eyes with greater AMD severity and especially in eyes with SDD both at baseline and at 4 years. The RIT prolongation as a measure of changing DA function may be a functional outcome measure in AMD clinical studies.

UV Protection by Natural Products: C. myrrha Oil Versus Sunscreen.

Exposure to various types of ultraviolet (UV) radiation from the sun has been linked to skin cancer. Use of sunscreen can reduce the damaging and carcinogenic effects of UV radiation. However, multiple chemicals in sunscreen can trigger allergic responses, making people less inclined to use sunscreen. Thus, finding natural, plant-based alternatives to sunscreen with similar efficacy has become an important area of research. Myrrh oil, extracted from the shrub Commiphora myrrha, has been used in the treatment of topical wounds and studies have shown that it may provide protection against solar radiation. This study sought to further investigate if C. myrrha oil can confer protection against UV radiation. A UV-sensitive strain of Saccharomyces cerevisiae was grown in petri dishes with one half covered by aluminum foil and the other half covered by clear polyethylene food wrap. The polyethylene half was treated with either SPF 15 or SPF 30 sunscreen, C. myrrha oil or a combination of C. myrrha oil and either sunscreen. The plates were exposed to sunlight. Colony death was quantified using visual estimation. While UV blocking by C. myrrha oil alone was not as effective as that by the synthetic sunscreen, the 1:1 combination of C. myrrha oil and SPF 15 sunblock was significantly more effective than SPF 15 sunblock alone to prevent S. cerevisiae death. These data suggest that naturally-based sunscreens supplemented with synthetic UV deterrents may provide a more holistic approach to prevent UV-induced skin damage. J Drugs Dermatol. 2018;17(8):905-907.

Decreased Visual Function Scores on a Low Luminance Questionnaire Is Associated with Impaired Dark Adaptation.

PURPOSE: We investigate whether responses on a Low Luminance Questionnaire (LLQ) in patients with a range of age-related macular degeneration (AMD) severity are associated with their performance on focal dark adaptation (DA) testing and with choroidal thickness. DESIGN: Cross-sectional, single-center, observational study. PARTICIPANTS: A total of 113 participants older than 50 years of age with a range of AMD severity. METHODS: Participants answered the LLQ on the same day they underwent DA testing using a focal dark adaptometer measuring rod intercept time (RIT). We performed univariable and multivariable analyses of the LLQ scores and age, RIT, AMD severity, subfoveal choroidal thickness [SFCT], phakic status, and best-corrected visual acuity. MAIN OUTCOME MEASURES: The primary outcome of this study was the score on the 32-question LLQ. Each item in the LLQ is designated to 1 of 6 subscales describing functional problems in low luminance: driving, emotional distress, mobility, extreme lighting, peripheral vision, and general dim lighting. Scores were computed for each subscale, in addition to a weighted total mean score. RESULTS: Responses from 113 participants (mean age, 76.2±9.3 years; 58.4% were female) and 113 study eyes were analyzed. Univariable analysis demonstrated that lower scores on all LLQ subscales were correlated with prolonged DA testing (longer RIT) and decreased choroidal thickness. All associations were statistically significant except for the association of choroidal thickness and "peripheral vision." The strongest association was the LLQ subscale of driving with RIT (r =-0.97, P < 0.001). Multivariable analysis for each of the LLQ subscale outcomes, adjusted for age, included RIT, with total LLQ score, "driving," "extreme lighting," and "mobility" also including choroidal thickness. In all multivariable analyses, RIT had a stronger association than choroidal thickness. CONCLUSIONS: This cross-sectional analysis demonstrates associations of patient-reported functional deficits, as assessed on the LLQ, with both reduced DA and reduced choroidal thickness, in a population of older adults with varying degrees of AMD severity and good visual acuity in at least 1 eye. These analyses suggest that local functional measurements of DA testing (RIT) and choroidal thickness are associated with patient-reported functional deficits.

Molecular signatures of human induced pluripotent stem cells highlight sex differences and cancer genes.

Although human induced pluripotent stem cells (hiPSCs) have enormous potential in regenerative medicine, their epigenetic variability suggests that some lines may not be suitable for human therapy. There are currently few benchmarks for assessing quality. Here we show that X-inactivation markers can be used to separate hiPSC lines into distinct epigenetic classes and that the classes are phenotypically distinct. Loss of XIST expression is strongly correlated with upregulation of X-linked oncogenes, accelerated growth rate in vitro, and poorer differentiation in vivo. Whereas differences in X-inactivation potential result in epigenetic variability of female hiPSC lines, male hiPSC lines generally resemble each other and do not overexpress the oncogenes. Neither physiological oxygen levels nor HDAC inhibitors offer advantages to culturing female hiPSC lines. We conclude that female hiPSCs may be epigenetically less stable in culture and caution that loss of XIST may result in qualitatively less desirable stem cell lines.

Amelogenin-assisted ex vivo remineralization of human enamel: Effects of supersaturation degree and fluoride concentration.

The formation of organized nanocrystals that resemble enamel is crucial for successful enamel remineralization. Calcium, phosphate and fluoride ions, and amelogenin are important ingredients for the formation of organized hydroxyapatite (HAP) crystals in vitro. However, the effects of these remineralization agents on the enamel crystal morphology have not been thoroughly studied. The objective of this study was to investigate the effects of fluoride ions, supersaturation degree and amelogenin on the crystal morphology and organization of ex vivo remineralized human enamel. Extracted third molars were sliced thin and acid-etched to provide the enamel surface for immersion in different remineralization solutions. The crystal morphology and mineral phase of the remineralized enamel surface were analyzed by field emission-scanning electron microscopy, attenuated total reflection-Fourier transformed infrared and X-ray diffraction. The concentration of fluoride and the supersaturation degree of hydroxyapatite had significant effects on the crystal morphology and crystal organization, which varied from plate-like loose crystals to rod-like densely packed nanocrystal arrays. Densely packed arrays of fluoridated hydroxyapatite nanorods were observed under the following conditions: σ(HAP)=10.2±2.0 with 1.5±0.5 mg l(-1) fluoride and 40±10 µg ml(-1) amelogenin, pH 6.8±0.4. A phase diagram summarizes the conditions that form dense or loose hydroxyapatite nanocrystal structures. This study provides the basis for the development of novel dental materials for caries management.