Analysis of hedgehog signaling in periocular sebaceous carcinoma

PURPOSE: Sebaceous carcinoma (SC) is a clinical masquerader of benign conditions resulting in significant eye morbidity, sometimes leading to extensive surgical treatment including exenteration, and even mortality. Little is known about the genetic or molecular basis of SC. This study identifies the involvement of Hedgehog (Hh) signaling in periocular SC. METHODS: Fifteen patients with periocular SC patients were compared to 15 patients with eyelid nodular basal cell carcinoma (nBCC; a known Hh tumor), alongside four normal individuals as a control for physiological Hh expression. Expression of Patched 1 (PTCH1), Smoothened (SMO), and glioma-associated zinc transcription factors (Gli1 and Gli2) were assessed in histological sections using immunohistochemistry and immunofluorescence (IF) techniques. Antibody specificity was verified using Western-blot analysis of a Gli1 over-expressed cancer cell line, LNCaP-Gli1. Semi-quantification compared tumors and control tissue using IF analysis by ImageJ software. RESULTS: Expression of the Hh pathway was observed in SC for all four major components of the pathway. PTCH1, SMO, and Gli2 were more significantly upregulated in SC (P < 0.01) compared to nBCC. Stromal expression of PTCH1 and Gli2 was observed in SC (P < 0.01). In contrast, stromal expression of these proteins in nBCC was similar or down-regulated compared to physiological Hh controls. CONCLUSIONS: The Hh signaling pathway is significantly more upregulated in periocular SC compared to nBCC, a known aberrant Hh pathway tumor. Furthermore, the stroma of the SC demonstrated Hh upregulation, in particular Gli2, compared to nBCC. Targeting of this pathway may be a potential treatment strategy for SC

Intraocular Pressure Changes Following Stand-Alone Phacoemulsification: An IRISɌ Registry Analysis

To describe real-world intraocular pressure (IOP) changes following stand-alone cataract surgery by comparing postoperative IOP to phakic fellow eyes. Retrospective clinical cohort study. A total of 1,334,868 patients (336,060 with glaucoma and 998,808 without glaucoma) in the IRIS® Registry (Intelligent Research in Sight) underwent stand-alone phacoemulsification from 1 January 2013 to 30 September 2019 with a fellow eye that had subsequent cataract surgery. Postoperative daily mean IOP was compared between surgical and control eyes from postoperative day 1 to 90. A generalized linear model determined when the postoperative daily mean IOP stabilized to calculate a final mean IOP, which was then compared to baseline IOP. Postoperative daily mean IOP was initially greater for surgical than for control eyes because of an early postoperative IOP spike. By postoperative day 13, postoperative daily mean IOP was significantly lower for surgical than for control eyes every day through postoperative day 90 (P < .001). There was a mean (SD) decrease from baseline to final mean IOP of 1.55 (3.52) mm Hg or 7.79% for all surgical eyes, 1.91 (3.93) mm Hg or 8.89% for surgical eyes with glaucoma, and 1.37 (3.28) mm Hg or 7.24% for surgical eyes without glaucoma, respectively. There was a statistically significant decrease from baseline to the final mean IOP for all surgical eyes, surgical eyes without glaucoma, and all categories of pre-glaucoma and glaucoma (P < .0001 for all, excluding uveitic glaucoma [P = .0016]). Eyes both with and without glaucoma that underwent stand-alone phacoemulsification had a significant decrease in IOP through the 90-day postoperative period compared to baseline and phakic fellow eyes. •There is an initial spike in intraocular pressure following stand-alone cataract surgery.•Intraocular pressure then declines and settles to significantly lower than baseline.•This intraocular pressure response is greater for eyes with glaucoma

Predictors of intraocular pressure response and survival after phacoemulsification for glaucomatous eyes in the IRIS registry (Intelligent Research in Sight)

This retrospective cohort study describes the real-world incidence and maintenance of clinically meaningful intraocular pressure (IOP) reduction (“response”) following stand-alone phacoemulsification for 667,987 eyes with suspected or confirmed glaucoma in the IRIS Registry (Intelligent Research in Sight) from 1/1/2013–9/30/2019. Intraocular pressure responders had ≥ 20% IOP reduction in daily mean IOP from baseline on two consecutive postoperative visits. We declared failure if a responder no longer maintained ≥ 20% IOP reduction. The estimated IOP responder rate was 41.3% by Kaplan–Meier analysis. Multivariate analysis demonstrated relationships between IOP response and baseline IOP (hazard ratio (HR) (95% confidence interval)) 1.48 (1.48–1.49), per 3 mmHg, P < 0.0001), age (HR 1.14 (1.13–1.14), per 10 years, P < 0.0001), male sex (HR 1.13 (1.12–1.15), P < 0.0001), prostaglandin analogue (HR 0.88 (0.87–0.90), P < 0.0001), and Rho-kinase inhibitor use (HR 1.50 (1.32–1.70), P = 0.01). Fifty percent of IOP responders failed at a median time of 14.3 months. Multivariate analysis demonstrated relationships between failure and baseline IOP (HR 0.75 (0.75–0.76), per 3 mmHg, P < 0.0001), nitric oxide donating prostaglandin (HR 1.78 (1.46–2.18), P < 0.0001) and Rho-kinase inhibitor use (HR 1.73 (1.43–2.09), P < 0.0001). Clinicians may counsel glaucoma patients with risk factors on whether to anticipate an IOP response and its expected duration after stand-alone phacoemulsification

Risk of Musculoskeletal Injuries, Fractures, and Falls in Medicare Beneficiaries With Disorders of Binocular Vision

IMPORTANCE: Disorders of binocular vision are increasingly prevalent among fee-for-service Medicare beneficiaries 65 years or older. Visual impairment is a recognized risk factor for fractures. Despite the association of visual impairment and fracture risk, to our knowledge, no study has examined the influence that disorders of binocular vision (strabismus, amblyopia, diplopia, and nystagmus) may have on musculoskeletal injury and fracture risk in the elderly population. OBJECTIVE: To evaluate associations between disorders of binocular vision and musculoskeletal injury, fracture, and falls in the elderly. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 10-year (2002-2011) musculoskeletal injury, fracture, or fall prevalence in a 5% random sample of Medicare Part B fee-for-service claims for beneficiaries with disorders of binocular vision. Participants included Medicare beneficiaries living in the general community who were 65 years or older with at least 1 year of Medicare Part B enrollment. EXPOSURES: Diagnosis of a disorder of binocular vision. MAIN OUTCOMES AND MEASURES: Ten-year prevalence of musculoskeletal injury, fracture, or fall in individuals with and without disorders of binocular vision. Analyses were adjusted for age, sex, race/ethnicity, region of residence, systemic and ocular comorbidities, and duration of follow-up. RESULTS: There were 2 196 881 Medicare beneficiaries identified. Of these, 99 525 (4.5%) had at least 1 reported disorder of binocular vision (strabismus, 2.3%; diplopia, 2.2%; amblyopia, 0.9%; and nystagmus, 0.2%). During the 10-year study period, there were 1 272 948 (57.9%) patients with documented musculoskeletal injury, fracture, or fall. The unadjusted odds ratio (OR) for the association between disorders of binocular vision and any of the 3 injury types was 2.23 (95% CI, 2.20-2.27; P < .001). The adjusted OR was 1.27 (95% CI, 1.25-1.29; P < .001). CONCLUSIONS AND RELEVANCE: Medicare beneficiaries with a disorder of binocular vision have significantly higher odds of sustaining a musculoskeletal injury, fracture, or fall. This finding is an important step forward in understanding and developing strategies to prevent these injuries, which are associated with high morbidity in the elderly

Risk of Musculoskeletal Injuries, Fractures, and Falls in Medicare Beneficiaries With Disorders of Binocular Vision

ImportanceDisorders of binocular vision are increasingly prevalent among fee-for-service Medicare beneficiaries 65 years or older. Visual impairment is a recognized risk factor for fractures. Despite the association of visual impairment and fracture risk, to our knowledge, no study has examined the influence that disorders of binocular vision (strabismus, amblyopia, diplopia, and nystagmus) may have on musculoskeletal injury and fracture risk in the elderly population.ObjectiveTo evaluate associations between disorders of binocular vision and musculoskeletal injury, fracture, and falls in the elderly.Design, setting, and participantsA retrospective study of 10-year (2002-2011) musculoskeletal injury, fracture, or fall prevalence in a 5% random sample of Medicare Part B fee-for-service claims for beneficiaries with disorders of binocular vision. Participants included Medicare beneficiaries living in the general community who were 65 years or older with at least 1 year of Medicare Part B enrollment.ExposuresDiagnosis of a disorder of binocular vision.Main outcomes and measuresTen-year prevalence of musculoskeletal injury, fracture, or fall in individuals with and without disorders of binocular vision. Analyses were adjusted for age, sex, race/ethnicity, region of residence, systemic and ocular comorbidities, and duration of follow-up.ResultsThere were 2,196,881 Medicare beneficiaries identified. Of these, 99,525 (4.5%) had at least 1 reported disorder of binocular vision (strabismus, 2.3%; diplopia, 2.2%; amblyopia, 0.9%; and nystagmus, 0.2%). During the 10-year study period, there were 1,272,948 (57.9%) patients with documented musculoskeletal injury, fracture, or fall. The unadjusted odds ratio (OR) for the association between disorders of binocular vision and any of the 3 injury types was 2.23 (95% CI, 2.20-2.27; P &lt; .001). The adjusted OR was 1.27 (95% CI, 1.25-1.29; P &lt; .001).Conclusions and relevanceMedicare beneficiaries with a disorder of binocular vision have significantly higher odds of sustaining a musculoskeletal injury, fracture, or fall. This finding is an important step forward in understanding and developing strategies to prevent these injuries, which are associated with high morbidity in the elderly

Intraocular Pressure Spike Following Stand-Alone Phacoemulsification in the Intelligent Research in Sight (IRIS®) Registry

To evaluate risk factors for intraocular pressure (IOP) spike following cataract surgery using the IRIS® Registry (Intelligent Research in Sight). Retrospective clinical cohort study. Adults with IRIS® Registry data who underwent stand-alone phacoemulsification from January 1, 2013 to September 30, 2019. IOP spike was defined as a postoperative IOP >30 mmHg and >10 mmHg from baseline within the first postoperative week. Odds ratios (OR) for demographic and clinical characteristics were calculated with univariate and multivariate logistic regression analyses. Incidence and OR of IOP spike. We analyzed data from 1,191,034 eyes (mean age 71.3 years, 61.2% female sex and 24.8% with glaucoma). An IOP spike occurred in 3.7% of all eyes, 5.2% of eyes with glaucoma and 3.2% of eyes without glaucoma (P<0.0001). Multivariable analyses of all eyes indicated a greater risk of IOP spike with higher baseline IOP (OR 1.57 per 3 mmHg), male sex (OR 1.79), glaucoma (OR 1.19), Black race (OR 1.39 compared to Asian and OR 1.21 compared to Hispanic), older age (OR 1.07 per 10 years), and complex surgery coding (OR 1.22, all P<0.0001). Diabetes (OR 0.90) and aphakia after surgery (OR 0.60) appeared to be protective against IOP spike (both P<0.0001). Compared to glaucoma suspects, there was a greater risk of IOP spike with ocular hypertension (OR 1.55), pigmentary glaucoma (OR 1.56), and pseudoexfoliative glaucoma (OR 1.52), and less risk for normal tension glaucoma (OR 0.55), primary angle closure (PAC) suspect (OR 0.67), and PAC glaucoma (OR 0.81, all P<0.0001). More baseline glaucoma medications was associated with IOP spike (OR 1.18 per medicine) while topical beta-blocker use (OR 0.68) was protective (both P<0.0001). Higher baseline IOP, male sex, glaucoma, Black race, older age, and complex cataract coding were associated with an early postoperative IOP spike whereas diabetes and postoperative aphakia were protective against a spike following stand-alone phacoemulsification. Glaucomatous eyes demonstrated different risk profiles dependent on subtype of glaucoma. The findings may help surgeons stratify and mitigate the risk of IOP spike after cataract surgery

Adoption and perceptions of electronic health record systems by ophthalmologists: An American Academy of Ophthalmology survey

Objective To assess the current state of electronic health record (EHR) use by ophthalmologists, including adoption rate and user satisfaction. Design Population-based, cross-sectional study. Participants A total of 592 members of the American Academy of Ophthalmology (AAO) participated. Methods A total of 3796 AAO members were randomly selected on the basis of geography and solicited to participate in a study of EHR adoption. Among those solicited, 392 members completed a web-based version of the survey and 200 members completed a telephone-based version. The survey included sections assessing the current level of EHR adoption, the value of various EHR features, the practice demographics, and, for participants with an EHR, the details of their system. Responses were collected and analyzed using univariate statistical tests. Main Outcome Measures Current adoption rate of EHRs, user satisfaction with EHRs, and importance of various EHR features to both users and nonusers. Results Overall, 12% of the practices surveyed had already implemented an EHR, 7% were in the process of doing so, and another 10% had plans to do so within 12 months. Both EHR users and nonusers rated the same EHR features as having the most value to their practices, and the 2 groups rated options for simplifying the EHR selection process similarly. Among those with an EHR in their practice, 69% were satisfied or extremely satisfied with their system, 64% reported increased or stable overall productivity, 51% reported decreased or stable overall costs, and 76% would recommend an EHR to a fellow ophthalmologist. Conclusions The adoption rate of EHRs by ophthalmology practices is low but comparable to that seen in other specialties. The satisfaction of those ophthalmologists already using an EHR is high. Because EHRs are part of the rapidly changing health information technology marketplace, the AAO Medical Information Technology Committee is planning to update these results on a regular basis. Financial Disclosure(s) The authors have no proprietary or commercial interest in any materials discussed in this article

The use of bevacizumab and ranibizumab for branch retinal vein occlusion in medicare beneficiaries

Purpose: To describe the frequency and variation of intravitreal bevacizumab and ranibizumab use for branch retinal vein occlusion (BVO) in the United States (US). Methods: We obtained a 5% random sample of Medicare beneficiaries from the Medicare Denominator and Physician/Supplier Part B claims files from 2010 to 2013 and identified all beneficiaries with an ICD-9-CM code for branch retinal vein occlusion (BVO, 362.36). Patient age, gender, race, state of residence and Charlson Comorbidity Index (CCI) scores were collected. Healthcare Common Procedure Coding System (HSCPS) codes for bevacizumab (J3590, J9035, and J3490) and for ranibizumab (J2778) were used to identify the mode of treatment for each patient. Patients who met the following criteria were excluded from this study: (1) under 65 years of age; (2) residence outside of the 50 United States or the District of Columbia; (3) no Part-B coverage or with HMO coverage that was not processed by Centers for Medicare & Medicaid Services (CMS); (4) concomitant diagnosis of diabetic edema (ICD-9: 362.07) or central retinal vein occlusion (ICD-9: 362.35); and (5) received both or none of the above two treatments. Geographic variation was examined by comparing injection frequencies across the nine US census divisions using Chi-squared analysis. Results: During 2010–2013, a majority of the 3944 BVO patients who met the inclusion criteria received bevacizumab compared to ranibizumab (76.7% vs 23.3%). Most patients were aged 75–79 (22.0%) or 80–84 (22.0%), female (61.5%), white (88.3%), and had a CCI score of 1–2 (39.8%). The frequencies of bevacizumab and ranibizumab injections for BVO varied significantly between the US census divisions (p < 0.0001). The highest frequencies of bevacizumab use were in the Mountain (90.6%) and Pacific (82.7%) divisions while the highest frequencies of ranibizumab use were in the West North Central (37.9%) and Mid Atlantic (32.7%) divisions. Conclusions and Importance: A majority of Medicare beneficiaries with BVO received bevacizumab compared to ranibizumab from 2010 to 2013, with significant geographic variation in the use of the two anti-VEGF agents. Future research into factors driving geographic variation in the use of these agents may help direct cost-effective strategies for the management of BVO. Keywords: Branch retinal vein occlusion, BVO, Anti-VEGF, Geographic variation, Medicar

The use of bevacizumab and ranibizumab for branch retinal vein occlusion in medicare beneficiaries

PurposeTo describe the frequency and variation of intravitreal bevacizumab and ranibizumab use for branch retinal vein occlusion (BVO) in the United States (US).MethodsWe obtained a 5% random sample of Medicare beneficiaries from the Medicare Denominator and Physician/Supplier Part B claims files from 2010 to 2013 and identified all beneficiaries with an ICD-9-CM code for branch retinal vein occlusion (BVO, 362.36). Patient age, gender, race, state of residence and Charlson Comorbidity Index (CCI) scores were collected. Healthcare Common Procedure Coding System (HSCPS) codes for bevacizumab (J3590, J9035, and J3490) and for ranibizumab (J2778) were used to identify the mode of treatment for each patient. Patients who met the following criteria were excluded from this study: (1) under 65 years of age; (2) residence outside of the 50 United States or the District of Columbia; (3) no Part-B coverage or with HMO coverage that was not processed by Centers for Medicare &amp; Medicaid Services (CMS); (4) concomitant diagnosis of diabetic edema (ICD-9: 362.07) or central retinal vein occlusion (ICD-9: 362.35); and (5) received both or none of the above two treatments. Geographic variation was examined by comparing injection frequencies across the nine US census divisions using Chi-squared analysis.ResultsDuring 2010-2013, a majority of the 3944 BVO patients who met the inclusion criteria received bevacizumab compared to ranibizumab (76.7% vs 23.3%). Most patients were aged 75-79 (22.0%) or 80-84 (22.0%), female (61.5%), white (88.3%), and had a CCI score of 1-2 (39.8%). The frequencies of bevacizumab and ranibizumab injections for BVO varied significantly between the US census divisions (p &lt; 0.0001). The highest frequencies of bevacizumab use were in the Mountain (90.6%) and Pacific (82.7%) divisions while the highest frequencies of ranibizumab use were in the West North Central (37.9%) and Mid Atlantic (32.7%) divisions.Conclusions and importanceA majority of Medicare beneficiaries with BVO received bevacizumab compared to ranibizumab from 2010 to 2013, with significant geographic variation in the use of the two anti-VEGF agents. Future research into factors driving geographic variation in the use of these agents may help direct cost-effective strategies for the management of BVO