Sociodemographic Disparities in Preoperative Visual Acuity and Cataract Surgery Utilization in the San Francisco Bay Area.

OBJECTIVE: We examined whether cataract surgery utilization and preoperative visual acuity were associated with patient-specific factors, including ocular findings and comorbidities, general biomedical factors, and/or sociodemographic factors. DESIGN: Retrospective, cross-sectional study. SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: We reviewed the electronic health records of patients from 2012 to 2022 who were examined and followed for at least 2 years by an eye care provider at University of California San Francisco Health (UCSF Health) and who had cataract in at least one eye associated with best-corrected visual acuity of 20/25 or worse. Data include ocular factors (e.g., best-corrected visual acuity, lens opacity grade, diagnoses of glaucoma, and/or age-related macular degeneration), biomedical comorbidities, and sociodemographic factors including race/ethnicity, health insurance coverage, primary language spoken, and social vulnerability index. METHODS: Logistic and multivariate regression analyses. MAIN OUTCOME MEASURES: We examined cataract surgery utilization and preoperative best-corrected visual acuity. RESULTS: Compared to White and Asian patients, Black patients had the lowest rates of cataract surgery utilization and the poorest mean preoperative visual acuities, with Hispanic patients following in second place in both categories. However, when the analysis controlled for sociodemographic and biomedical factors, Medicaid insurance and speaking Chinese as a primary language emerged as significant associations. In addition, higher cataract surgery utilization rates were associated with worse preoperative best-corrected visual acuity, a concurrent diagnosis of glaucoma, and a concurrent diagnosis of macular degeneration. Worse preoperative visual acuity was associated with Spanish or Chinese language preference, Medicaid status, and glaucoma diagnosis; poorer preoperative visual acuity was only weakly correlated with increased social vulnerability. CONCLUSIONS: After adjusting for other biomedical and sociodemographic variables, having Medicaid insurance and being a non-English speaker were the factors most notably associated with reduced cataract surgery utilization and poorer preoperative visual acuity. Health insurance and language barriers, as well as other biomedical and sociodemographic factors, may explain a large proportion of the racial disparities in both cataract surgery utilization and preoperative visual acuity observed among Black and Hispanic patients. Chinese-speaking patients with limited English proficiency are a vulnerable subgroup that exhibits lower rates of cataract surgery utilization and higher degrees of visual loss prior to undergoing cataract surgery compared to other Asian patients.

Differential Effects of Race/Ethnicity and Social Vulnerability on COVID-19 Positivity, Hospitalization, and Death in the San Francisco Bay Area.

BACKGROUND: Higher COVID-19 incidence and morbidity have been documented for US Black and Hispanic populations but not as clearly for other racial and ethnic groups. Efforts to elucidate the mechanisms underlying racial health disparities can be confounded by the relationship between race/ethnicity and socioeconomic status. OBJECTIVE: Examine race/ethnicity and social vulnerability effects on COVID-19 outcomes in the San Francisco Bay Area, an ethnically and socioeconomically diverse region, using geocoded patient records from 2020 in the University of California, San Francisco Health system. KEY RESULTS: Higher social vulnerability, but not race/ethnicity, was associated with less frequent testing yet a higher likelihood of testing positive. Asian hospitalization rates (11.5%) were double that of White patients (5.4%) and exceeded the rates for Black (9.3%) and Hispanic patients (6.9%). A modest relationship between higher hospitalization rates and increasing social vulnerability was evident only for White patients. Hispanic patients had the highest years of expected life lost due to COVID-19. CONCLUSIONS: COVID-19 outcomes were not consistently explained by greater social vulnerability. Asian individuals showed disproportionately high rates of hospitalization regardless of social vulnerability status. Study of the San Francisco Bay Area population not only provides valuable insights into the differential contributions of race/ethnicity and social determinants of health to COVID-19 outcomes but also emphasizes that all racial groups have experienced the toll of the pandemic, albeit in different ways and to varying degrees.

Racial/Ethnic, Biomedical, and Sociodemographic Risk Factors for COVID-19 Positivity and Hospitalization in the San Francisco Bay Area.

BACKGROUND: The COVID-19 pandemic has uncovered clinically meaningful racial/ethnic disparities in COVID-19-related health outcomes. Current understanding of the basis for such an observation remains incomplete, with both biomedical and social/contextual variables proposed as potential factors. PURPOSE: Using a logistic regression model, we examined the relative contributions of race/ethnicity, biomedical, and socioeconomic factors to COVID-19 test positivity and hospitalization rates in a large academic health care system in the San Francisco Bay Area prior to the advent of vaccination and other pharmaceutical interventions for COVID-19. RESULTS: Whereas socioeconomic factors, particularly those contributing to increased social vulnerability, were associated with test positivity for COVID-19, biomedical factors and disease co-morbidities were the major factors associated with increased risk of COVID-19 hospitalization. Hispanic individuals had a higher rate of COVID-19 positivity, while Asian persons had higher rates of COVID-19 hospitalization. The excess hospitalization risk attributed to Asian race was not explained by differences in the examined biomedical or sociodemographic variables. Diabetes was an important risk factor for COVID-19 hospitalization, particularly among Asian patients, for whom diabetes tended to be more frequently undiagnosed and higher in severity. CONCLUSION: We observed that biomedical, racial/ethnic, and socioeconomic factors all contributed in varying but distinct ways to COVID-19 test positivity and hospitalization rates in a large, multi-racial, socioeconomically diverse metropolitan area of the United States. The impact of a number of these factors differed according to race/ethnicity. Improving overall COVID-19 health outcomes and addressing racial and ethnic disparities in COVID-19 outcomes will likely require a comprehensive approach that incorporates strategies that target both individual-specific and group contextual factors.

CENTRAL RETINAL ARTERY OCCLUSION WITH CILIORETINAL ARTERY SPARING AFTER LASER-ASSISTED IN SITU KERATOMILEUSIS.

PURPOSE: To report a central retinal artery occlusion with cilioretinal artery sparing in a 48-year-old woman after laser-assisted in situ keratomileusis surgery. METHODS: Case history and clinical examination including best-corrected visual acuity, serum markers, slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, fluorescein angiography, and optical coherence tomography. RESULTS: A 48-year-old woman underwent routine laser-assisted in situ keratomileusis surgery in both eyes. On postoperative Day 1, vision was 20/20 in both eyes with full visual fields by confrontation. Eight hours after being examined, she reported photopsias and a new visual field defect in the right eye . Visual acuity was 20/40, pinhole 20/20 in the right eye, with restriction of visual field by confrontation. Dilated fundus examination revealed retinal whitening in all quadrants with sparing of the fovea along the distribution of a perfused cilioretinal artery. Optical coherence tomography showed an intact foveal depression with inner retinal layer hyperreflectivity outside the region of the perfused cilioretinal artery. Fluorescein angiography revealed sectoral nonperfusion of the posterior pole with macular sparing along the patent cilioretinal artery. Hypercoagulable workup, carotid imaging, and magnetic resonance imaging of the brain were unremarkable. CONCLUSION: This is the first report of a central retinal artery occlusion with cilioretinal artery sparing occurring on postoperative Day 1 after laser-assisted in situ keratomileusis surgery.

Author Correction: Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Content validity of a novel patient-reported and observer-reported outcomes assessment to evaluate ocular symptoms associated with infectious conjunctivitis in both adult and pediatric populations.

BACKGROUND: Acute infectious conjunctivitis is a common condition most frequently caused by viruses or bacteria. Clinical outcome assessments have been used to assess signs and symptoms of bacterial and viral conjunctivitis, but have not been evaluated for content validity. We aimed to develop content-valid patient- (PRO) and observer-reported outcome (ObsRO) instruments to assess symptoms of ocular discomfort associated with viral or bacterial conjunctivitis in adult and pediatric patients. METHODS: Draft items were developed from a previous review of published studies from 2001 to 2015. Patients and caregivers of patients with a diagnosis of viral or bacterial conjunctivitis within the past 6 months were recruited. Concept elicitation with open-ended questions explored signs and symptoms, followed by cognitive interviewing to assess clarity and relevance of the draft items. Patients aged ≥8 years were interviewed for the PRO; parents/caregivers of children aged 1-10 years were interviewed for the ObsRO. Interviews were conducted in three rounds to allow changes. Concept saturation was documented using a saturation grid. Cognitive interview data were analyzed iteratively and focused on clarity, relevance and inconsistent interpretation of the instrument's content. RESULTS: Overall, 23 patients or parents/caregivers participated (round 1, n = 10; round 2, n = 6; round 3, n = 7). Data saturation was reached by the 16th interview. The most frequent spontaneously reported signs/symptoms were: discharge, red/pink eyes, itchiness, swelling/puffiness, watery eyes, pain, burning and foreign body sensation. Itching, pain/burning/stinging and foreign body sensation were most commonly reported as the top three most bothersome symptoms. Interview results indicated that items on pain, itching and foreign body sensation for the PRO and pain or discomfort for the ObsRO were relevant to the patients' experience of conjunctivitis and were clear and easy to understand. CONCLUSIONS: PRO and ObsRO items were found to be clear, relevant and appropriate in assessing key viral and bacterial conjunctivitis symptoms in adult and pediatric patients.

Aberrant DNA methylation of miRNAs in Fuchs endothelial corneal dystrophy.

Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically, miR-199B is extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199B hypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.

One-Year Efficacy and Safety of Combined Photorefractive Keratectomy and Accelerated Corneal Collagen Cross-Linking after Intacs SK Intracorneal Ring Segment Implantation in Moderate Keratoconus.

PURPOSE: To report one-year outcomes of a modified version of two-stage multimodal surgical protocol for moderate keratoconus which has been suggesting promising preliminary results. MATERIALS AND METHODS: 30 eyes of 25 patients with moderate keratoconus who exhibited visual complaints and/or disease progression were included for this retrospective case study. Approximately 3 months after implantation of intracorneal ring segment (Intacs SK™), a combination of corneal wavefront-guided transepithelial photorefractive keratectomy (CWG-transPRK, Schwind Amaris® 1050, and Schwind Sirius) and accelerated collagen cross-linking (accCXL, Avedro KXL™) was performed. Patients were examined for uncorrected and corrected distance visual acuity (UDVA; CDVA), keratometric power (K), corneal thickness, and corneal higher-order aberrations (HOAs) preoperatively and at postoperative 1, 3, 6, and 12 months. RESULTS: The median UDVA and mean CDVA were enhanced from 6/38 to 6/12 and from 6/19 to 6/7.5, respectively, through 12 months after CWG-transPRK/accCXL. The 12-month CDVA of all patients was better than 6/12 Snellen, and no subject lost one or more lines of CDVA. The magnitudes of both myopia and corneal steepness were decreased in turn by Intacs SK implantation and also by CWG-transPRK/accCXL, but the reduction in HOA was largely the result of CWG-transPRK/accCXL. The magnitude of corneal thinning stabilized within 3 months after CWG-transPRK/accCXL. CONCLUSION: This approach may allow patients with moderate keratoconus to obtain satisfactory vision without the need for contact lens wear. This surgery appeared to be effective and safe through 1 year of follow-up.

Overexpression of MMPs in Corneas Requiring Penetrating and Deep Anterior Lamellar Keratoplasty.

Purpose: Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis. Methods: Protein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas. Results: Luminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients. Conclusions: Multiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization.

Necrotizing Scleritis After Cosmetic Conjunctivectomy With Mitomycin C.

PURPOSE: To report cases of necrotizing scleritis, a sight-threatening complication that can result from cosmetic conjunctivectomy procedures. DESIGN: Retrospective case series. METHODS: The medical records of consecutive patients who underwent eye-whitening conjunctivectomy with mitoycin C (MMC) treatment performed by 1 surgeon in South Korea and were referred to the authors' clinic between January 2011 and December 2015 were reviewed. The patients in whom findings of necrotizing scleritis with active inflammation were detected in an avascular area of previous conjunctivectomy were included. RESULTS: Of a total of 231 patients who had received cosmetic eye whitening, 4 patients who met the inclusion criteria were identified. The average length of time from cosmetic eye surgery to a diagnosis of necrotizing scleritis was 51 months and all patients had unilateral findings of necrotizing scleritis. There was no underlying systemic autoimmunity or infectious etiology in all cases. Three of these 4 patients were treated with a conjunctival flap; however, all 4 received systemic anti-inflammatory treatment with oral corticosteroids. The mean follow-up duration of the patients was 22.75 months. CONCLUSIONS: Necrotizing scleritis is a severe complication that can arise after cosmetic eye-whitening conjunctivectomy with MMC. Because of the large area of the ocular surface that is treated in eye-whitening with MMC, the necrotizing scleritis that can ensue may be more extensive and severe than the surgically induced necrotizing scleritis following other periocular surgeries such as pterygium removal. Proper anti-inflammatory treatment and surgical intervention should be required for management of this complication.

Performance of Bio-Occlusive Dressing as Barrier Protection from Presurgical Chlorhexidine Skin Preparation.

Purpose/Aim of the study: Chlorhexdine has been shown to provide excellent and cost-effective presurgical antisepsis. However, standard presurgical concentrations of chlorhexidine (2-4%) are known to cause ocular injury, even in cases in which a bio-occlusive dressing (Tegaderm™) was applied beforehand to the closed eye. MATERIALS AND METHODS: Three experiments were conducted to assess the barrier performance of Tegaderm™ to chlorhexidine skin prep in vitro and on non-ocular skin. The experiments used water as a control group. RESULTS: In the first in vitro experiment, the chlorhexidine group showed penetration at the edges of the Tegaderm™ at 5 minutes while the water (control) group never penetrated the Tegaderm™. A subsequent experiment testing the central permeability of the tegaderm showed it to be impermeable to both chlorhexidine and water after 90 minutes. In the in vivo experiment, the chlorhexidine group showed penetration at 10 minutes, while the water (control) group never penetrated the Tegaderm™. CONCLUSIONS: These data suggest Tegaderm™ is permeable at the edges to chlorhexidine but not water. Based on this, along with reports of ocular injury from chlorhexidine skin preparation of the head despite prior application of Tegaderm™ over the eyes, we advise against using bio-occlusive adhesive dressing to protect the ocular surface from chlorhexidine exposure. We suggest an alternative presurgical antiseptic agent such as povidone-iodine be employed whenever possible.

Late extrusion of intrastromal corneal ring segments: A report of two cases.

PURPOSE: To report two cases of patients with late extrusion following uneventful implantation of intrastromal corneal ring segments (ICRS) for myopia. OBSERVATIONS: Two patients with previously implanted ICRS for low myopia presented with spontaneous onset of extrusion of their ICRS, one at 7 years post-operatively and the other at 17 and 20 years. Both cases underwent explantation and maintained excellent best-corrected visual acuity. These cases represent the longest reported intervals between implantation of the ICRS and subsequent extrusion. CONCLUSIONS AND IMPORTANCE: Late extrusion can occur many years following implantation of ICRS, even in eyes without pre-existing thinning or ectasia. The technique for explantation described herein can result in favorable clinical outcomes in such cases. These cases demonstrate the importance of long-term follow up of eyes that have undergone ICRS implantation.

Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic Calcifications Using a Nitinol Loop: A Case Series.

Deposition of dystrophic calcifications on the posterior surface of silicone intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis. Accumulation of silicone oil droplets on the posterior surface of silicone IOLs in silicone-filled eyes has also been reported. Recently, a novel technique to manually remove dystrophic calcifications using a nickel titanium loop (Finesse Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL exchange. Here, the authors report their outcomes with this technique in five eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

Comprehensive characterization of DNA methylation changes in Fuchs endothelial corneal dystrophy.

Transparency of the human cornea is necessary for vision. Fuchs Endothelial Corneal Dystrophy (FECD) is a bilateral, heritable degeneration of the corneal endothelium, and a leading indication for corneal transplantation in developed countries. While the early onset, and rarer, form of FECD has been linked to COL8A2 mutations, the more common, late onset form of FECD has genetic mutations linked to only a minority of cases. Epigenetic modifications that occur in FECD are unknown. Here, we report on and compare the DNA methylation landscape of normal human corneal endothelial (CE) tissue and CE from FECD patients using the Illumina Infinium HumanMethylation450 (HM450) DNA methylation array. We show that DNA methylation profiles are distinct between control and FECD samples. Differentially methylated probes (10,961) were identified in the FECD samples compared with the control samples, with the majority of probes being hypermethylated in the FECD samples. Genes containing differentially methylated sites were disproportionately annotated to ontological categories involving cytoskeletal organization, ion transport, hematopoetic cell differentiation, and cellular metabolism. Our results suggest that altered DNA methylation patterns may contribute to loss of corneal transparency in FECD through a global accumulation of sporadic DNA methylation changes in genes critical to basic CE biological processes.

Corneal Injury from Presurgical Chlorhexidine Skin Preparation.

BACKGROUND: Chlorhexidine skin preparation has been shown to provide highly effective antimicrobial presurgical skin cleansing. However, there is a significant risk of ocular toxicity when it is used in periocular areas. CASE DESCRIPTION: We describe 2 cases of significant corneal damage resulting from 4% chlorhexidine gluconate preoperative skin cleanser, despite the use of protective occlusive dressing over the eyes. Because of the potential for severe corneal toxicity resulting from use of chlorhexidine, alternative agents such as 10% povidone-iodine should be considered for skin preparation near periocular areas whenever possible. CONCLUSIONS: If chlorhexidine gluconate must be employed near periocular areas, great care must be exercised to avoid contact with the eyes, and additional protective measures (e.g., absorbent eye pads along with tightly occlusive dressings) must be used whenever possible.

Upside-down lens syndrome: ocular complications secondary to inverted implantation of the Kelman Multiflex anterior chamber intraocular lens.

PURPOSE: To describe ocular complications resulting from inverted insertion of a Kelman Multiflex anterior chamber intraocular lens (ACIOL). DESIGN: Retrospective observational case series. METHODS: We describe the outcomes of 4 cases of complicated cataract surgery in which a flexible open-loop polymethylmethacrylate (PMMA) ACIOL (Kelman Multiflex type) was placed in an inverted configuration, all of which were referred to a single institution. RESULTS: In all 4 cases, the placement of an inverted ACIOL resulted in ocular complications including chronic iritis, cystoid macular edema, pupil capture, iris adhesions, and corneal decompensation. CONCLUSIONS: Inadvertent inverted placement of the Kelman Multiflex anterior chamber intraocular lenses can lead to a constellation of severe ocular complications. When inserting such lenses, the surgeon should ensure that the lens is correctly oriented such that the optic vaults anteriorly and not posteriorly.

Pharmacokinetics of azithromycin and moxifloxacin in human conjunctiva and aqueous humor during and after the approved dosing regimens.

PURPOSE: To evaluate the ocular pharmacokinetics of azithromycin and moxifloxacin in human conjunctiva and aqueous humor in subjects undergoing cataract surgery. DESIGN: Multicenter, open-label, randomized study. METHODS: Subjects scheduled for routine cataract surgery and with normal-appearing conjunctiva were eligible. One conjunctival biopsy sample and 1 aqueous humor sample were obtained from subjects randomly assigned to 1 of 10 prespecified time points (1 to 312 hours) after treatment initiation of azithromycin ophthalmic solution 1% or moxifloxacin ophthalmic solution 0.5%. Samples were assayed using liquid chromatography tandem mass spectrometry. RESULTS: Azithromycin 1% provided high concentrations (peak level, 559.7 µg/g) in human conjunctiva that were sustained at levels 1 to 2 orders of magnitude higher than those of moxifloxacin 0.5% throughout the 7-day dosing period and for at least 7 days thereafter. Azithromycin also showed an extended half-life (65.7 hours) in conjunctiva relative to that of moxifloxacin (28.6 hours). Accordingly, the concentration of azithromycin was maintained well above the minimum inhibitory concentration required for inhibition of growth of 90% of tested bacterial isolates for at least 7 days, whereas moxifloxacin conjunctival levels fell to levels at or less than the minimum inhibitory concentration required for inhibition of growth of 90% of tested bacterial isolates approximately 24 hours after the last dose. Peak aqueous humor concentration of moxifloxacin was higher (0.77 µg/mL) than that of azithromycin (0.053 µg/mL). No clinically relevant safety findings were observed. CONCLUSIONS: Azithromycin 1% demonstrated high, therapeutic levels in the conjunctiva that were maintained up to 7 days after completion of a 1-week dosing regimen. Aqueous humor levels, however, were subtherapeutic with this dosing regimen. In comparison, moxifloxacin achieved lower conjunctival tissue levels, but higher aqueous humor levels.

Acute angle-closure glaucoma due to iris transfixation of a subluxated posterior chamber intraocular lens-capsular bag complex.

An 80-year-old woman with pseudoexfoliation syndrome developed subluxation of a posterior chamber intraocular lens (IOL)-capsular bag complex due to zonular rupture. She underwent a limited 25-gauge pars plana vitrectomy and iris transfixation of the subluxated IOL-capsule complex. The postoperative course was uneventful until the patient developed acute angle-closure glaucoma 3 weeks postoperatively. Ultrasound biomicroscopy confirmed pupillary block by the IOL-capsule complex. The patient was treated with intraocular pressure-lowering medications and a vitreous tap before a laser peripheral iridotomy could be performed successfully. The vision returned to normal, and the angle closure resolved. We recommend that a prophylactic surgical iridectomy be performed in patients with iris transfixation of a posterior chamber IOL-capsular bag complex.