Comparison of Machine and Human Expert Evaluation of Capsulorrhexis Creation Performance Through Analysis of Surgical Video Recordings.

Purpose: Achieving competency in cataract surgery is an essential component of ophthalmology residency training. Video-based analysis of surgery can change training through its objective, reliable, and timely assessment of resident performance. Methods: Using the Image Labeler application in MATLAB, the capsulorrhexis step of 208 surgical videos, recorded at the University of Michigan, was annotated for subjective and objective analysis. Two expert surgeons graded the creation of the capsulorrhexis based on the International Council of Ophthalmology's Ophthalmology Surgical Competency Assessment Rubric:Phacoemulsification (ICO-OSCAR:phaco) rating scale and a custom rubric (eccentricity, roundness, size, centration) that focuses on the objective aspects of this step. The annotated rhexis frames were run through an automated analysis to obtain objective scores for these components. The subjective scores were compared using both intra and inter-rater analyses to assess the consistency of a human-graded scale. The subjective and objective scores were compared using intraclass correlation methods to determine relative agreement. Results: All rhexes were graded as 4/5 or 5/5 by both raters for both items 4 and 5 of the ICO-OSCAR:phaco rating scale. Only roundness scores were statistically different between the subjective graders (mean difference = -0.149, p-value = 0.0023). Subjective scores were highly correlated for all components (>0.6). Correlations between objective and subjective scores were low (0.09 to 0.39). Conclusion: Video-based analysis of cataract surgery presents significant opportunities, including the ability to asynchronously evaluate performance and provide longitudinal assessment. Subjective scoring between two raters was moderately correlated for each component.

Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

NO EFFECT OF REAL-WORLD UNIVERSAL FACE MASKING ON POST-INTRAVITREAL INJECTION ENDOPHTHALMITIS RATE AT A SINGLE TERTIARY ACADEMIC CENTER.

PURPOSE: To determine whether universal masking during COVID-19 altered rate and outcomes of postinjection endophthalmitis. METHODS: Retrospective, single-site, comparative, cohort study. Eyes diagnosed with endophthalmitis within 4 weeks of intravitreal injection at the University of Michigan from August 1, 2012, to November 15, 2022, were identified. Cases were considered "masking" between March 15, 2020, and November 15, 2022. Endophthalmitis rate, visual acuity, and microbial spectrum were investigated. RESULTS: There were 20 postinjection endophthalmitis cases out of 72,194 injections (0.028%; one in 3,571 injections) premasking and 10 of 38,962 with universal masking (0.026%; one in 3,846 injections; odds ratio 0.9; 95% [confidence interval]: 0.4-2.0). Referral from the community was unchanged with 32 cases referred premasking (0.35 cases/month) and 10 cases with masking (0.31 cases/month). Presenting mean the logarithm of the minimum angle of resolution visual acuity with masking of all postinjection endophthalmitis cases trended worse (2.35 ± 0.40) compared with premasking (2.09 ± 0.48; P = 0.05) with light perception visual acuity more common with masking (31.6% vs. 10.9%, P = 0.06). There was no delay in time from procedure to initial treatment ( P = 0.36), no difference in the rate of initial treatment with tap and inject (T/I), and similar positive-culture rates ( P = 0.77) between the cohorts. Visual acuity after 30 days of follow-up was clinically unchanged (∼20/500 vs. 20/400; P = 0.59). CONCLUSION: Universal masking had no effect on postinjection endophthalmitis rate or on the rate of culture-positive cases. Although presenting visual acuity appeared worse with masking, this was not statistically significant, and current treatment paradigms resulted in similar visual outcomes.

Systolic Blood Pressure and Survival to Very Old Age. Results from the Women's Health Initiative.

Background: The association between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine survival probabilities to age 90 for various SBP levels among women aged ≥ 65 years with or without BP medication. Methods: We analyzed blood pressure data from participants in the Women's Health Initiative (n=16,570) who were aged 65 or older and without history of cardiovascular disease, diabetes or cancer. Blood pressure was measured at baseline (1993-1998) and then annually through 2005. The outcome was defined as survival to age 90 with follow-up until February 28, 2020. Results: During a follow-up of 18 years, 9,723 (59%) of 16,570 women survived to age 90. The SBP associated with the highest probability of survival was about 120mmHg regardless of age. Compared to an SBP between 110 and 130 mmHg, women with uncontrolled SBP had a lower survival probability across all age groups and with or without BP medication. A 65-year-old women on BP medication with an interpolated SBP between 110 and 130 mmHg in 80% of the first 5 years of follow-up had a 31% (95% confidence interval, 24%, 38%) absolute survival probability. For those with 20% time in range, the probability was 21% (95% confidence interval, 16%, 26%). Conclusions: An SBP level below 130 mmHg was found to be associated with longevity among older women. The longer SBP was controlled at a level between 110 and 130 mmHg, the higher the survival probability to age 90. Preventing age-related rises in SBP and increasing the time with controlled BP levels constitute important measures for achieving longevity.

A Novel CD206 Targeting Peptide Inhibits Bleomycin-Induced Pulmonary Fibrosis in Mice.

Activated M2-polarized macrophages are drivers of pulmonary fibrosis in several clinical scenarios, including Idiopathic Pulmonary Fibrosis (IPF). In this study, we investigated the effects of targeting the CD206 receptor in M2-like macrophages with a novel synthetic analogue of a naturally occurring Host Defense Peptide (HDP), RP-832c, to decrease profibrotic cytokines. RP-832c selectively binds to CD206 on M2-polarized bone marrow-derived macrophages (BMDM) in vitro, resulting in a time-dependent decrease in CD206 expression and a transient increase in M1-macrophage marker TNF-α. To elucidate the antifibrotic effects of RP-832c, we used a murine model of bleomycin (BLM)-induced early-stage pulmonary fibrosis. RP-832c significantly reduced fibrosis in a dose-dependent manner, and decreased CD206, TGF-ß1, and α-SMA expression in mouse lungs. Similarly, in an established model of lung fibrosis, RP-832c significantly decreased lung fibrosis and significantly decreased inflammatory cytokines TNF-α, IL-6, IL-10, IFN-γ, CXCL1/2, and fibrosis markers TGF-ß1 and MMP-13. In comparison with the FDA-approved drugs Nintedanib and Pirfenidone, RP-832c exhibited a similar reduction in fibrosis compared to Pirfenidone, and to a greater extent than Nintedanib, with no apparent toxicities observed. In summary, our findings showed that inhibiting the profibrotic alternatively activated M2-like macrophages using a novel peptide, RP-832c, could reduce BLM-induced pulmonary fibrosis in mice, warranting the therapeutic potential of this peptide for patients with pulmonary fibrosis.

Association of Artificially Sweetened Beverage Consumption and Urinary Tract Cancers in the Women's Health Initiative Observational Study.

Background: Insufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers. Objective: We sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages. Design setting and participants: This was a secondary analysis of data from the Women's Health Initiative Observational Study, a multicenter longitudinal prospective study of the health of 93 676 postmenopausal women with a mean follow-up time of 13.5 yr. Women were identified at 40 clinical centers across the USA and enrolled from 1993 to 1998. Women between the ages of 50 and 79 yr were enrolled. We included women who answered questions about artificially sweetened beverage consumption and reported no prior urinary tract cancer diagnoses. The frequency of artificially sweetened beverage consumption was categorized as follows: rare artificially sweetened beverage consumption (never to fewer than one serving per week), frequent consumption (one to six servings per week), and daily consumption (more than one servings per day). Outcome measurements and statistical analysis: The incidence of urinary tract cancer reported during subsequent visits until February 28, 2020 was recorded. Demographic characteristics were compared between those with varying levels of artificially sweetened beverage consumption. Descriptive statistics were used to report the rates of urinary tract cancer diagnosis, and Cox regression models were constructed to determine hazard ratios and adjust for potential confounders. Results and limitations: We identified 80 388 participants who met the inclusion criteria. Most participants (64%) were infrequent consumers of artificially sweetened beverages, with 13% (n = 10 494) consuming more than one servings per day. The incidence of urinary tract cancers was low, with only 804 cases identified. Cox regression models showed that frequent artificially sweetened beverage consumption was associated with a higher risk of kidney cancer (adjusted hazard ratio 1.34, 95% confidence interval 1.03-1.75). There was no significant association between artificially sweetened beverage intake and bladder cancer. Conclusions: Frequent consumption of artificially sweetened beverages may be associated with a higher risk of kidney cancer among postmenopausal women. Patient summary: A secondary analysis of the Women's Health Initiative Observational Study showed that higher consumption of artificially sweetened beverages was associated with a higher risk of kidney cancer.

Proton Pump Inhibitor Use and Obesity-Associated Cancer in the Women's Health Initiative.

Proton pump inhibitors (PPIs) have off-target activity on fatty acid synthase (FASN), a critical enzyme in energy balance and cancer growth. We evaluated risk of common obesity-related cancers: breast, colorectal (CRC), and endometrial, with use of PPI and histamine-2 receptor antagonists (H2RA) in 124,931 postmenopausal women enrolled in the Women's Health Initiative. Incident cancer cases were physician-adjudicated. Cox proportional hazards models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for cancer incidence after year 3. There were 7956 PPI ever users and 9398 H2RA only users. Ever use of either PPI or H2RA was not associated with risk of breast cancer (n = 9186) nor risk of endometrial cancer (n = 1231). The risk of CRC (n = 2280) was significantly lower in PPI users (HR = 0.75, 95% CI = 0.61-0.92), but not in H2RA users (HR = 1.13, 95% CI = 0.97-1.31). The association of PPI use with CRC was apparent regardless of BMI or NSAID use, and was stronger with longer PPI duration (p = 0.006) and potency (p = 0.005). The findings that PPI use, but not H2RA use, demonstrate an inverse dose-response relationship with risk of CRC is consistent with preclinical data showing FASN inhibition prevents colon cancer progression and supports a role of PPI in CRC prevention.

Small airways dysfunction is associated with increased exacerbations in patients with asthma.

There is a poor understanding of why some patients with asthma experience recurrent exacerbations despite high levels of treatment. We compared measurements of peripheral ventilation heterogeneity and respiratory system mechanics in participants with asthma who were differentiated according to exacerbation history, to ascertain whether peripheral airway dysfunction was related to exacerbations. Three asthmatic groups: "stable" (no exacerbations for >12 mo, n = 18), "exacerbation-prone" (≥1 exacerbation requiring systemic corticosteroids within the last 12 mo, but stable for ≥1-mo, n = 9), and "treated-exacerbation" (exacerbation requiring systemic corticosteroids within the last 1 mo, n = 12) were studied. All participants were current nonsmokers with <10 pack yr smoking history. Spirometry, static lung volumes, ventilation heterogeneity from multibreath nitrogen washout (MBNW), and respiratory system mechanics from oscillometry were measured. The exacerbation-prone group compared with the stable group had slightly worse spirometry [forced expired volume in 1 s or FEV1 z-score -3.58(1.13) vs. -2.32(1.06), P = 0.03]; however, acinar ventilation heterogeneity [Sacin z-score 7.43(8.59) vs. 3.63(3.88), P = 0.006] and respiratory system reactance [Xrs cmH2O·s·L-1 -2.74(3.82) vs. -1.32(1.94), P = 0.01] were much worse in this group. The treated-exacerbation group had worse spirometry but similar small airway function, compared with the stable group. Patients with asthma who exacerbate have worse small airway function as evidenced by increases in Sacin measured by MBNW and ΔXrs from oscillometry, both markers of small airway dysfunction, compared with those that do not.NEW & NOTEWORTHY This study assessed the relationship between peripheral airway function, measured by multiple breath nitrogen washout and oscillometry impedance, and exacerbation history. We found that those with a history of exacerbation in the last year had worse peripheral airway function, whereas those recently treated for an asthma exacerbation had peripheral airway function that was comparable to the stable group. These findings implicate active peripheral airway dysfunction in the pathophysiology of an asthma exacerbation.

Assessing patient perception of risk in ocular stem cell therapies.

A wide variety of stem cell-derived therapies are under development for the treatment of retinal degeneration. In order to better understand patient perspectives about these therapies, we assessed risk tolerance using an in-person survey of 178 patients at an academic eye center. Risk of malignancy served as a hypothetical, readily understood, and serious adverse event to be considered in trade for potential visual improvement from a stem cell-derived treatment. The results indicate that patients were willing to trade visual improvement against a risk of malignancy that far exceeds actual risk. Two novel findings were that older patients and those with an intermediate level of visual loss were particularly risk tolerant. The quantitative survey results provide a step toward understanding patient perspectives that will, over the long term, guide the development of ocular stem cell-derived therapies.

Visual Outcomes in Surgically Treated Intracranial Meningiomas.

BACKGROUND: Intracranial meningiomas that arise from the medial sphenoid ridge, anterior clinoid process, tuberculum sellae, or planum sphenoidale often impair vision by compressing the optic nerves and optic chiasm. Although many studies have reported visual outcome following surgery for these tumors, documentation has often been incomplete and not validated by patient self-report. METHODS: Retrospective study of 40 patients drawn from a single, academic, medical center. We used a unique method of assessing visual outcome based on whether the change in visual function affected the preoperatively better-sighted or worse-sighted eye in the belief that this method would correlate with effects on activities of daily living (ADL). To elicit patient self-reports of those effects, we conducted telephone interviews of 25 patients with a standard questionnaire. We also assessed putative ophthalmic, imaging, and surgical predictors of visual outcome. RESULTS: Visual improvement occurred in 61% of patients with preoperative monocular visual dysfunction, but only 22% of patients reported improvement in their ability to conduct ADL, and 17% lost vision. Visual outcomes were better in patients with preoperative binocular visual dysfunction, where visual improvement occurred in 73% and no patient lost vision in the preoperatively better-sighted eye. However, only 27% of patients with preoperative binocular visual dysfunction reported improvement in their ability to conduct ADL. Long duration of vision impairment, presence of optic disc pallor, large tumor size, and imaging-based preoperative optic canal involvement did not preclude a favorable visual outcome. Aggressive surgical reduction in displacement of the optic nerves was not necessary to obtain a favorable visual outcome and sometimes led to an unfavorable visual outcome. CONCLUSIONS: In this study, surgery often improved vision, especially in patients with preoperative binocular visual dysfunction. But patients indicated that the effect on their ability to perform ADL was more modest. Moreover, 17% of patients with preoperative monocular visual dysfunction lost vision in the only affected eye, often to a considerable degree. In those patients, surgery would be justified primarily to relieve the concern of having a large brain tumor and to prevent tumor growth. Preoperative ophthalmic and imaging features poorly predicted visual outcomes. Favorable visual outcomes occurred without aggressive surgical debulking of the tumors.

Imaging Errors in Distinguishing Pituitary Adenomas From Other Sellar Lesions.

BACKGROUND: Pituitary adenomas and nonadenomatous lesions in the sellar region may be difficult to distinguish by imaging yet that distinction is critical in guiding management. The nature of the diagnostic errors in this setting has not been well documented. METHODS: Two neurosurgeons and 2 neuroradiologists of differing experience levels viewed deidentified MRIs of 18 nonadenomatous sellar lesions and 21 adenomas. They recorded their diagnoses, the imaging features they used to make those diagnoses, and their confidence in making those diagnoses. RESULTS: Among the 18 nonadenoma cases, 11 (61%) were incorrectly diagnosed as adenoma by at least 1 reader, including Rathke cleft cyst, plasmacytoma, aneurysm, craniopharyngioma, chordoma, Langerhans cell histiocytosis, metastasis, and undifferentiated sinonasal carcinoma. Among the 21 adenoma cases, 8 (38%) were incorrectly diagnosed by at least 1 reader as craniopharyngioma, Rathke cleft cyst, sinonasal carcinoma, hemangioblastoma, and pituitary hyperplasia. Incorrect imaging diagnoses were made with high confidence in 13% of readings. Avoidable errors among the nonadenomatous cases occurred when readers failed to appreciate that the lesion was separate from the pituitary gland. Unavoidable errors in those cases occurred when the lesions were so large that the pituitary gland had been obliterated or the imaging features of a nonadenomatous lesion resembled those of a cystic pituitary adenoma. Avoidable errors in misdiagnosis of adenomas as nonadenomas occurred when readers failed to appreciate features highly characteristic of adenomas. An unavoidable error occurred because a cystic adenoma had features correctly associated with craniopharyngioma. CONCLUSIONS: Errors in imaging differentiation of pituitary adenoma from nonadenomatous lesions occurred often and sometimes with high confidence among a small sample of neurosurgeons and neuroradiologists. In the misdiagnosis of nonadenomatous lesions as adenomas, errors occurred largely from failure to appreciate a separate pituitary gland, but unavoidable errors occurred when large lesions had obliterated this distinguishing feature. In the misdiagnosis of adenomas as nonadenomatous lesions, avoidable errors occurred because readers failed to recognize imaging features more characteristic of adenomas and because cystic adenomas share features with craniopharyngiomas and Rathke cleft cysts. Awareness of these errors should lead to improved management of sellar lesions.

Trends in Glaucoma Surgeries Performed by Glaucoma Subspecialists versus Nonsubspecialists on Medicare Beneficiaries from 2008 through 2016.

PURPOSE: To characterize the use of laser and incisional glaucoma surgeries among Medicare beneficiaries from 2008 through 2016 and to compare the use of these surgeries by glaucoma subspecialists versus nonsubspecialists. DESIGN: Retrospective, observational analysis. PARTICIPANTS: Medicare beneficiaries (n = 1 468 035) undergoing ≥1 laser or incisional glaucoma surgery procedure during 2008 through 2016. METHODS: Claims data from a 20% sample of enrollees in fee-for-service Medicare throughout the United States were analyzed to identify all laser and incisional glaucoma surgeries performed from 2008 through 2016. We assessed use of traditional incisional glaucoma surgery techniques (trabeculectomy and glaucoma drainage implant [GDI] procedure) and microinvasive glaucoma surgery (MIGS). Enrollee and procedure counts were multiplied by 5 to estimate use throughout all of Medicare. Linear regression was used to compare trends in use of glaucoma surgeries between ophthalmologists who could be characterized as glaucoma subspecialists versus nonsubspecialists. MAIN OUTCOME MEASURES: Numbers of laser and incisional glaucoma surgeries performed overall and stratified by glaucoma subspecialist status. RESULTS: The number of Medicare beneficiaries undergoing any glaucoma therapeutic procedure increased by 10.6%, from 218 375 in 2008 to 241 565 in 2016. The total number of traditional incisional glaucoma surgeries decreased by 11.7%, from 37 225 to 32 885 (P = 0.02). The total number of MIGS procedures increased by 426% from 13 705 in 2012 (the first year MIGS codes were available) to 58 345 in 2016 (P = 0.001). Throughout the study period, glaucoma subspecialists performed most of the trabeculectomies (76.7% in 2008, 83.1% in 2016) and GDI procedures (77.7% in 2008, 80.6% in 2016). Many MIGS procedures were performed by nonsubspecialists. The proportions of endocyclophotocoagulations, iStent (Glaukos; San Clemente, CA) insertions, goniotomies, and canaloplasties performed by glaucoma subspecialists in 2016 were 22.0%, 25.2%, 56.9%, and 62.8%, respectively. CONCLUSIONS: From 2008 through 2016, a large shift in practice from traditional incisional glaucoma surgeries to MIGS procedures was observed. Although glaucoma subspecialists continue to perform most traditional incisional glaucoma surgeries, many MIGS procedures are performed by nonsubspecialists. These results highlight the importance of training residents in performing MIGS procedures and managing these patients perioperatively. Future studies should explore the impact of this shift in care on outcomes and costs.

Differences in Cataract Surgery Rates Based on Dementia Status.

BACKGROUND: Cataract surgery substantially improves patient quality of life. Despite the rising prevalence of dementia in the US, little is known about use of cataract surgery among this group. OBJECTIVE: To evaluate the relationship between dementia status and cataract surgery. METHODS: Using administrative insurance claims for a representative sample of 1,125,387 US Medicare beneficiaries who received eye care between 2006 and 2015, we compared cataract surgery rates between patients with and without dementia via multivariable regression models to adjust for patient characteristics. Main outcome measures were annual rates of cataract surgery and hazard ratio and 95% confidence interval (CI) for receiving cataract surgery. RESULTS: Cataract surgery was performed in 457,128 patients, 23,331 with a prior diagnosis of dementia. 16.7% of dementia patients underwent cataract surgery, compared to 43.8% of patients without dementia. 59 cataract surgeries were performed per 1000 dementia patients annually, versus 105 surgeries per 1000 nondementia patients. After adjusting for patient characteristics, dementia patients were approximately half as likely to receive cataract surgery compared to nondementia patients (adjusted HR = 0.53, 95% CI 0.53-0.54). Among the subset of patients who received a first cataract surgery, those with dementia were also less likely to receive second-eye cataract surgery (adjusted HR = 0.87, 95% CI 0.86-0.88). CONCLUSION: US Medicare patients with dementia are less likely to undergo cataract surgery than those without dementia. This finding has implications for quality of care and dementia progression. More information is necessary to understand why rates of cataract surgery are lower for these patients, and to identify conditions where benefits of surgery may outweigh risks.

A Comparison of Resource Use and Costs of Caring for Patients With Exfoliation Syndrome Glaucoma Versus Primary Open-Angle Glaucoma.

PURPOSE: To characterize differences in resource utilization and cost of managing enrollees with exfoliation glaucoma (XFG) compared to primary open-angle glaucoma (POAG). DESIGN: Retrospective utilization and cost comparison using Medicare claims data. METHODS: We identified Medicare beneficiaries with XFG or POAG and ≥5 years of continuous enrollment from January 2008 to December 2014. We distinguished newly diagnosed cases from those with preexisting disease. We compared ophthalmic resource utilization and costs over 2 years of follow-up for persons with newly diagnosed and preexisting XFG vs those with POAG. Main outcome measures were number of clinic visits, diagnostic procedures, medication fills, laser and incisional surgery, and mean eye care costs per beneficiary. RESULTS: Among 192 eligible enrollees (median age 77.6 years) with newly diagnosed XFG and 7339 enrollees (median age 77.3 years) with newly diagnosed POAG, those with XFG had more office visits (mean, 9.1 vs 7.9; P = .001), cataract surgery (34.9% vs 19.0%; P < .0001), and glaucoma surgery (28.7% vs 19.7%, P = .002). They also experienced 27% higher mean total eye care costs ($3260 vs $2562, P = .0001) over 2 years of follow-up. Among 2745 enrollees (median age 80.5 years) with preexisting XFG and 89 036 persons (median age 79.5) with preexisting POAG, persons with XFG had more office visits (mean 9.3 vs 7.3; P < .0001), perimetry (85.3% vs 79.8%; P < .0001), cataract surgery (23.4% vs 12.3%; P < .0001), laser trabeculoplasty (18.6% vs 9.6%; P < .0001), and trabeculectomy (8.1 vs 1.8%; P < .0001) and experienced 37% higher total mean eye care costs ($3764 vs $2739; P < .0001). CONCLUSIONS: Healthcare resource utilization and costs are substantially higher for managing patients with XFG compared to POAG.

Epigenetic markers in basal cell carcinoma: universal themes in oncogenesis and tumor stratification? - a short report.

BACKGROUND: Advanced basal cell carcinomas (BCCs) suffer from a scarcity of effective treatment options. Previously, we found that the targetable histone methyltransferase EZH2 was upregulated in aggressive BCC subtypes, suggesting that epigenetics may play a role in BCC progression. The purpose of this study was to determine whether EZH2-associated proteins and marks may be employed for the stratification of BCC histologic subtypes. METHODS: Sixty-two specimens (from 61 patients), representing more or less aggressive BCC histologic subtypes and matching non-malignant epidermal cells, were included in this study. Immunohistochemistry of H3K27me3, 5hmC, NSD2, MOF and JARID1B was performed to assess their putative associations with BCC histologic subtypes, as well as with EZH2 and Ki67 expression levels. RESULTS: We found that H3K27me3 and 5hmC upregulation was positively correlated with the occurrence of a less aggressive BCC histology. The modifications were also positively correlated with each other. Interestingly, we found that they were negatively correlated with the expression of EZH2, a marker for an aggressive BCC histology. The levels of NSD2, MOF, H3K27me3 and 5hmC were found to be universally upregulated in BCCs versus non-malignant epidermal cells. CONCLUSIONS: Our data reveal an EZH2-associated epigenetic marker profile that correlates with histologic signs of BCC aggressiveness. Our findings may have diagnostic and therapeutic implications, and indicate that epigenetic markers may be shared even with relatively less aggressive tumor types, thereby suggesting universal themes.

Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment.

Purpose: Retinal detachment (RD) separates the retina from the underlying retinal pigment epithelium, resulting in a gradual degeneration of photoreceptor (PR) cells. It is known that RD also results in an inflammatory response, but its contribution to PR degeneration is unknown. In this study we examine the inflammatory responses to RD in patient vitreous and validate a mouse experimental RD as a model of this phenomenon. Methods: Multiplex bead arrays were used to examine cytokine levels in vitreous samples from 24 patients with macula-off rhegmatogenous retinal detachment (RRD) undergoing reattachment surgery and from 10 control patients undergoing vitrectomy for vitreous opacities or epiretinal membrane. Activation of the innate immune response was then examined in a mouse model of RD. Results: Twenty-eight factors were significantly increased in vitreous from RD patients versus controls. Notable were the cytokines MCP-1 (CCL2), IP-10 (CXCL10), fractalkine (CX3CL1), GRO (CXCL1), MDC (CCL22), IL-6, and IL-8, which all exhibited relatively high concentrations and several-fold increases in the vitreous of RD patients. Concentrations of various analytes correlated with a range of clinical variables such as duration of detachment and visual acuity. Retinal detachment in the mouse resulted in cytokine mRNA expression changes consistent with human RD vitreous results, as well as microglial proliferation and migration toward the outer retina. Conclusions: The findings suggest that an inflammatory response involving microglia is a component of the reaction to retinal detachment that may impact visual acuity after surgical repair and that mouse experimental RD can serve as a model to study this effect.

Access to Ophthalmologists in States Where Optometrists Have Expanded Scope of Practice.

Importance: As the United States considers how to best structure its health care services, specialty care availability is receiving increased focus. This study assesses whether patients lack reasonable access to ophthalmologists in states where optometrists have been granted expanded scope of practice. Objective: To determine the estimated travel time (ETT) to the nearest ophthalmologist office for persons residing in states that have expanded scope of practice for optometrists, and to quantify ETT to the nearest ophthalmologist for Medicare beneficiaries who received surgical care from optometrists in those states between 2008 and 2014. Design, Setting, and Participants: This study used data from the 2010 US census, a 2016 American Academy of Ophthalmology member database, and a data set of claims data for a random sample of 20% of beneficiaries enrolled in Medicare nationwide from 2008 to 2014 (n=14 063 725). Combining these sources with geographic information systems analysis, the ETT to the nearest ophthalmologist office was calculated for every resident of Kentucky, Oklahoma, and New Mexico. This study also assessed ETT to the nearest ophthalmologist for Medicare beneficiaries in those states who had received surgery from an optometrist from 2008 to 2014. Data analyses were conducted from July 2016 to July 2017. Main Outcomes and Measures: The proportion of residents of Kentucky, Oklahoma, and New Mexico who live within an ETT of 10, 30, 45, 60, or 90 minutes of the nearest ophthalmologist office. Results: The study included 4 339 367 Kentucky residents, 3 751 351 Oklahoma residents, and 2 059 179 New Mexico residents. Of these, 5 140 547 (50.6%) were female. Racial/ethnic composition included 7 154 847 people (70.5%) who were white, 640 608 (6.3%) who were black, and 1 418 246 (14.0%) who were Hispanic. The mean (SD) age was 37.8 (22.8) years. More than 75% of residents in the 3 states lived within an ETT of 30 minutes to the nearest ophthalmology office, and 94% to 99% of residents lived within an ETT of 60 minutes to the nearest ophthalmology office. Among Medicare beneficiaries who received surgery by optometrists, 58.3%, 51.1%, and 46.9% in Kentucky, Oklahoma, and New Mexico, respectively, lived within an ETT of 30 minutes from the nearest ophthalmologist office. Conclusions and Relevance: In the states where optometrists have expanded scope of practice, most residents lived within an ETT of 30 minutes of the nearest ophthalmologist office, as do half of Medicare beneficiaries who received surgical care from optometrists. These results can help inform policy makers when weighing the pros and cons of scope of practice expansion for optometrists.

Trends in the Screening and Treatment of Retinopathy of Prematurity.

OBJECTIVES: To determine the current practice patterns of retinopathy of prematurity (ROP) screening and treatment and the attitudes toward new screening and treatment modalities in level III and level IV NICUs, as reported by medical directors. METHODS: Surveys were mailed to the medical directors of 847 level III NICUs identified in the 2011 American Academy of Pediatrics directory in April 2015. In September 2015, responses were compared with American Academy of Pediatrics guidelines and previous reports. Within-sample comparisons were made by level, setting, size, and academic status. RESULTS: Respondents indicated that ROP screening is most often performed in their NICUs by pediatric and/or retina specialists (90%); retinal imaging devices are infrequently used (21%). Treatment is performed by pediatric (39%) and/or retina (57%) specialists in the NICU, usually under conscious sedation (60%). The most common treatment modality was laser photocoagulation (85%), followed by anti-vascular endothelial growth factor injection (20%). Some NICUs do not provide treatment services (28%), often due to a lack of ophthalmologists (78%). Respondents showed slightly more agreement (35%) than disagreement (25%) that a retinal imaging device could replace indirect ophthalmoscopy (40% were neutral). More respondents agreed than disagreed (30% vs 15%) that telemedicine for ROP screening is safe, but most were neutral (55%). CONCLUSIONS: Screening and treatment of ROP are not implemented uniformly in NICUs across the United States. Concerns regarding an insufficient ROP workforce are validated.

Incidence and Risk Factors for Developing Diabetic Retinopathy among Youths with Type 1 or Type 2 Diabetes throughout the United States.

PURPOSE: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM) among children and adolescents, little is known about their risk of developing diabetic retinopathy (DR). We sought to identify risk factors for DR in youths with diabetes mellitus, to compare DR rates for youths with type 1 diabetes mellitus (T1DM) and those with T2DM, and to assess whether adherence to DR screening guidelines promoted by the American Academy of Ophthalmology, American Academy of Pediatrics, and American Diabetes Association adequately capture youths with DR. DESIGN: Retrospective observational longitudinal cohort study. PARTICIPANTS: Youths aged ≤21 years with newly diagnosed T1DM or T2DM who were enrolled in a large US managed-care network. METHODS: In this study of youths aged ≤21 years with newly diagnosed T1DM or T2DM who were under ophthalmic surveillance, we identified the incidence and timing of DR onset. Kaplan-Meier survival curves assessed the timing of initial diagnosis of DR for participants. Multivariable Cox proportional hazard regression modeling identified factors associated with the hazard of developing DR. Model predictors were age and calendar year at initial diabetes mellitus diagnosis, sex, race/ethnicity, net worth, and glycated hemoglobin A1c fraction (HbA1c). MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing DR. RESULTS: Among the 2240 youths with T1DM and 1768 youths with T2DM, 20.1% and 7.2% developed DR over a median follow-up time of 3.2 and 3.1 years, respectively. Survival curves demonstrated that youths with T1DM developed DR faster than youths with T2DM (P < 0.0001). For every 1-point increase in HbA1c, the hazard for DR increased by 20% (HR = 1.20; 95% CI 1.06-1.35) and 30% (HR = 1.30; 95% CI 1.08-1.56) among youths with T1DM and T2DM, respectively. Current guidelines suggest that ophthalmic screening begin 3 to 5 years after initial diabetes mellitus diagnosis, at which point in our study, >18% of youths with T1DM had already received ≥1 DR diagnosis. CONCLUSIONS: Youths with T1DM or T2DM exhibit a considerable risk for DR and should undergo regular screenings by eye-care professionals to ensure timely DR diagnosis and limit progression to vision-threatening disease.

Comparison of Outcomes of Laser Trabeculoplasty Performed by Optometrists vs Ophthalmologists in Oklahoma.

IMPORTANCE: Oklahoma is one of the few states where optometrists have surgical privileges to perform laser trabeculoplasty (LTP). Optometrists in other states are lobbying to obtain privileges to perform LTP and other laser procedures. Little is known whether outcomes of patients undergoing this procedure by optometrists are similar to those undergoing LTP by ophthalmologists. OBJECTIVE: To compare outcomes of LTPs performed by ophthalmologists with those performed by optometrists to determine whether differences exist in the need for additional LTPs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective longitudinal cohort study used a health care claims database containing more than 1000 eyes of Medicare enrollees with glaucoma who underwent LTP in Oklahoma from January 1, 2008, through December 31, 2013. For each procedure, the data specify the type of eye care professional who performed the LTP. The rate of LTPs performed by ophthalmologists that required 1 or more additional LTPs in the same eye was compared with the rate of LTPs performed by optometrists. Regression models determined factors affecting risk of undergoing more than 1 LTP in the same eye. MAIN OUTCOMES AND MEASURES: Proportion of enrollees requiring additional LTPs, hazard ratio with 95% CIs of undergoing additional LTPs. RESULTS: A total of 1384 eyes of 891 eligible patients underwent LTP from January 1, 2008, through December 31, 2013. There were 1150 eyes that received LTP (83.1%) by an ophthalmologist and 234 eyes (16.9%) that had the procedure performed by an optometrist. The mean (SD) age at the initial LTP was 77.7 (7.5) years for enrollees with ophthalmologist-performed LTP and 77.6 (8.0) years for those with optometrist-performed LTP (P = .89). Among the 1384 eyes receiving LTP, 258 (18.6%) underwent more than 1 LTP in the same eye. The proportion of eyes undergoing LTP by an optometrist requiring 1 or more subsequent LTP session (35.9%) was more than double the proportion of eyes that received this procedure by an ophthalmologist (15.1%). Medicare beneficiaries undergoing LTP by optometrists had a 189% increased hazard of requiring additional LTPs in the same eye compared with those receiving LTP by ophthalmologists (hazard ratio, 2.89; 95% CI, 2.00-4.17; P < .001) after adjusting for potential confounders. CONCLUSIONS AND RELEVANCE: Considerable differences exist among the proportions of patients requiring additional LTPs comparing those who were initially treated by ophthalmologists with those initially treated by optometrists. Health policy makers should be cautious about approving laser privileges for optometrists practicing in other states until the reasons for these differences are better understood.