Turning the operating room into a mixed-reality environment: a prospective clinical investigation for cerebral aneurysm clipping.

OBJECTIVE: The overall aim of this study was to demonstrate the potential benefit of a novel mixed-reality-head-mounted display (MR-HMD) on the spatial orientation of surgeons. METHODS: In a prospective clinical investigation, the authors applied for the first time a new multicamera navigation technology in an operating room setting that allowed them to directly compare MR-HMD navigation to standard monitor navigation. In the study, which included 14 patients with nonruptured middle cerebral artery aneurysms, the authors investigated how intuitively and effectively surgical instruments could be guided in 5 different visual navigation conditions. RESULTS: The authors demonstrate that multicamera tracking can be reliably integrated in a clinical setting (usability score 1.12 ± 0.31). Moreover, the technology captures large volumes of the operating room, allowing the team to track and integrate different devices and instruments, including MR-HMDs. Directly comparing mixed-reality navigation to standard monitor navigation revealed a significantly improved intuition in mixed reality, leading to navigation times that were twice as fast (2.1×, p ≤ 0.01). Despite the enhanced speed, the same targeting accuracy (approximately 2.5 mm, freehand tool use) in comparison to monitor navigation could be observed. Intraoperative planning strategies with mixed reality clearly outperformed classic preoperative planning: surgeons scored the mixed-reality plan as the best trajectory in 63% of the cases (chance level 33%). CONCLUSIONS: The incorporation of mixed reality in neurosurgical operations marks a significant advancement in the field. The use of mixed reality in brain surgery enhances the spatial awareness of surgeons, enabling more instinctive and precise surgical interventions. This technological integration promises to refine the execution of complex procedures without compromising accuracy.

Government Regulation and Percutaneous Coronary Intervention Volume, Access and Outcomes: Insights From the Washington State Cardiac Care Outcomes Assessment Program.

Background It is unclear how to geographically distribute percutaneous coronary intervention (PCI) programs to optimize patient outcomes. The Washington State Certificate of Need program seeks to balance hospital volume and patient access through regulation of elective PCI. Methods and Results We performed a retrospective cohort study of all non-Veterans Affairs hospitals with PCI programs in Washington State from 2009 to 2018. Hospitals were classified as having (1) full PCI services and surgical backup (legacy hospitals, n=17); (2) full services without surgical backup (new certificate of need [CON] hospitals, n=9); or (3) only nonelective PCI without surgical backup (myocardial infarction [MI] access hospitals, n=9). Annual median hospital-level volumes were highest at legacy hospitals (605, interquartile range, 466-780), followed by new CON, (243, interquartile range, 146-287) and MI access, (61, interquartile range, 23-145). Compared with MI access hospitals, risk-adjusted mortality for nonelective patients was lower for legacy (odds ratio [OR], 0.59 [95% CI, 0.48-0.72]) and new-CON hospitals (OR, 0.55 [95% CI, 0.45-0.65]). Legacy hospitals provided access within 60 minutes for 90% of the population; addition of new CON and MI access hospitals resulted in only an additional 1.5% of the population having access within 60 minutes. Conclusions Many PCI programs in Washington State do not meet minimum volume standards despite regulation designed to consolidate elective PCI procedures. This CON strategy has resulted in a tiered system that includes low-volume centers treating high-risk patients with poor outcomes, without significant increase in geographic access. CON policies should re-evaluate the number and distribution of PCI programs.

Clinical Factors and Outcomes When Real-World Heart Teams Overruled STS Risk Scores in TAVR Cases.

Objectives: This study was conducted to determine why heart teams recommended transcatheter aortic valve replacement (TAVR) versus surgical AVR (SAVR) for patients at low predicted risk of mortality (PROM) and describe outcomes of these cases. Background: Historically, referral to TAVR was based predominately on the Society of Thoracic Surgeons (STS) risk model's PROM >3%. In selected cases, heart teams had latitude to overrule these scores. The clinical reasons and outcomes for these cases are unclear. Methods: Retrospective data were gathered for all TAVR and SAVR cases conducted by 9 hospitals between 2013 and 2017. Results: Cases included TAVR patients with STS PROM >3% (n = 2,711) and ≤3% (n = 415) and SAVR with STS PROM ≤3% (n = 1,438). Leading reasons for recommending TAVR in the PROM ≤3% group were frailty (57%), hostile chest (22%), severe lung disease (16%), and morbid obesity (13%), and 44% of cases had multiple reasons. Most postoperative and 30-day outcomes were similar between TAVR groups, but the STS PROM ≤3% group had a one-day shorter length of stay (2.5 ± 3.4 vs. 3.5 ± 4.7 days; p ≤ 0.001) and higher one-year survival (91.6% vs. 86.0%, p=0.002). In patients with STS PROM ≤3%, 30-day mortality was higher for TAVR versus SAVR (2.0% vs. 0.6%; p < 0.001). Conclusions: Heart teams recommended TAVR in patients with STS PROM ≤3% primarily due to frailty, hostile chest, severe lung disease, and/or morbid obesity. Similar postoperative outcomes between these patients and those with STS PROM >3% suggest that decisions to overrule STS PROM ≤3% were merited and may have reduced SAVR 30-day mortality rate.

Comparison of 26-mm Evolut and 23-mm Sapien 3 Valves in TAVR for Small Aortic Annulus.

BACKGROUND: Patients with small aortic annuli (SAA) are prone to higher post-transcatheter aortic valve replacement (TAVR) transvalvular gradients and development of prosthesis-patient mismatch (PPM). In many patients with SAA, the choice of TAVR valve commonly involves choosing between the 26-mm Medtronic Evolut 2 (ME26) or the 23-mm Edwards Sapien 3 valve (ES23). We compared echocardiographic and clinical outcomes in patients with SAA undergoing TAVR with either valve. METHODS: We queried the Providence St. Joseph Health Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry database for patients undergoing TAVR with either the ES23 or ME26 between July 2015 and December 2018 at 11 hospitals. Post-TAVR echocardiographic and clinical results in-hospital, at 1 month, and at 1 year were examined. High gradient (HG) was defined as mean gradient (MG) ≥20 mm Hg. RESULTS: We identified 1162 patients with SAA undergoing TAVR with either the ME26 (n = 233) or ES23 valve (n = 929). Baseline characteristics between groups were similar. At 1 month, the ME26 was associated with a lower MG than the ES23 (7.7 ± 4.7 mm Hg vs 13.1 ± 4.9 mm Hg; P<.001) and moderate or severe PPM (11% and 3% vs 27% and 13%; P<.001). Occurrence of HG at 1 year was lower with the ME26 valve vs the ES23 valve (0% vs 15%; P<.001). In-hospital and follow-up clinical outcomes to 1 year were similar for both groups. CONCLUSION: TAVR in SAA with the ME26 is associated with lower incidence of HG or PPM compared with the ES23. While clinical outcomes at 1 year were similar, the long-term implications of these findings remain unknown.

Propofol as a Drug of Diversion: Changing Disposal Practices to Reduce Risk.

BACKGROUND: Propofol is a drug of diversion because of its high-volume use, lack of prescribed control mechanisms, and accessibility. As a result, intensive care unit nurses and other health care professionals are placed at unnecessary risk. Decreasing the risk of drug diversion can save lives, licenses, and livelihoods. LOCAL PROBLEM: Objectives were to reduce the risk of drug diversion and diminish the environmental impact of medication discarded down the sink. Disposing of residual propofol into activated carbon pouches was successful and sustainable in operating rooms at the study institution. Literature findings supported this intervention because of propofol's potential for abuse, ongoing diversion events, ease of access, poor control mechanisms, lack of standardization, excessive waste, and ecological impact. METHODS: The intensive care unit with the highest propofol use was selected to replicate the propofol disposal process used in the operating rooms. Activated carbon pouches and bottle cap removal tools were located in each intensive care unit room at the nurses' workstation for ease of use. Audits of unsecured waste bins and staff surveys of institutional policy awareness, disposal processes, barriers, and concerns were completed before and after the intervention. RESULTS: Survey results determined significant concern for drug diversion risk. The pilot project displayed success: 44.1% of propofol bottles in waste bins were full before the intervention and 0% were full afterward. CONCLUSION: Following institutional approval, this propofol disposal process was replicated in all intensive care units and the emergency department in the study institution.

Temporal Trends in Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting: Insights From the Washington Cardiac Care Outcomes Assessment Program.

Background Patient selection and outcomes for percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) have changed over the past decade. However, there is limited information on outcomes for both revascularization strategies in the same population. The study evaluated temporal changes in risk profile, procedural characteristics, and clinical outcomes for PCI- and CABG-treated patients. Methods and Results We analyzed all PCI and isolated CABG between 2005 and 2017 in nonfederal hospitals in Washington State. Descriptive analysis was performed to evaluate temporal changes in risk profile and, risk-adjusted in-hospital mortality. Over the study period, 178 474 PCI and 36 592 CABG procedures were performed. PCI and CABG volume decreased by 2.9% and 22.6%, respectively. Compared with 2005-2009, patients receiving either form of revascularization between 2014 and 2017 had a higher prevalence of comorbidities including diabetes mellitus and hypertension and dialysis. Presentation with ST-segment-elevation myocardial infarction (17% versus 20%) and cardiogenic shock (2.4% versus 3.4%) increased for patients with PCI compared with CABG. Conversely, clinical acuity decreased for patients receiving CABG over the study period. From 2005 to 2017, mean National Cardiovascular Data Registry CathPCI mortality score increased for patients treated with PCI (20.1 versus 22.4, P<0.0001) and decreased for patients treated with CABG (18.8 versus 17.8, P<0.0001). Adjusted observed/expected in-hospital mortality ratio increased for PCI (0.98 versus 1.19, P<0.0001) but decreased for CABG (1.21 versus 0.74, P<0.0001) over the study period. Conclusions Clinical acuity increased for patients treated with PCI rather than CABG. This resulted in an increase in adjusted observed/expected mortality ratio for patients undergoing PCI and a decrease for CABG. These shifts may reflect an increased use of PCI instead of CABG for patients considered to be at high surgical risk.

Effects of three intravitreal injections of aflibercept on the ocular circulation in eyes with age-related maculopathy.

AIMS: To investigate changes in ocular perfusion following three consecutive intravitreal injections with aflibercept for treatment of neovascular age-related macular degeneration (nAMD). METHODS: The study included 20 eyes from 20 Caucasian patients with unilateral nAMD and 20 fellow eyes. All nAMD eyes were treated with standard intravitreal injection of aflibercept (IVA; 2 mg). Measurements of ocular perfusion at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). Measurements were conducted at baseline, 1 week after the first injection, at the time point of the second and third injection as well as 1 month after the third injection. RESULTS: In treated eyes, mean blur rate (the main output parameter of LSFG) in the ONH microvasculature and in the choroid was significantly reduced 1 week after the first IVA treatment. The effect persisted throughout the entire follow-up period (p<0.001). No change in ocular perfusion was observed in fellow eyes. CONCLUSIONS: IVA for treatment of nAMD leads to a reduction in perfusion of the ONH and the choroid in the treated eye with no apparent effect on the fellow eye.

Patterns of morphologic alteration correlate with vision in diabetic macular oedema: a cross-sectional evaluation of patients using the SAVE II protocol.

PURPOSE: We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management. METHODS: This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken. RESULTS: In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9 ± 8.2 years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p < 0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p = 0.065) and oedema types 3 and 4 (p = 0.13). CONCLUSION: There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters.

Aqueous humour cytokine changes during a loading phase of intravitreal ranibizumab or dexamethasone implant in diabetic macular oedema.

PURPOSE: To determine the effect of intravitreal ranibizumab and a dexamethasone implant on aqueous humour cytokine, protein and enzyme levels and to correlate findings to morphologic and functional changes. METHODS: In a prospective, randomized, controlled, double-blind study, patients with clinically significant diabetic macular oedema (CSME) were randomly allocated to receive either monthly intravitreal injections of ranibizumab (Lucentis, Novartis Pharma) or a single dexamethasone implant (Ozurdex, Pharm-Allergan) at baseline (BL). Aqueous humour samples were collected at BL and weeks 2, 8 and 20. RESULTS: The study included 18 eyes of 18 patients. In the dexamethasone implant group, soluble intercellular adhesion molecule 1 (sICAM-1) (weeks 2 and 8), CXCL9/monokine induced by gamma interferon (MIG) (weeks 2 and 8), soluble vascular cell adhesion protein 1 (sVCAM-1) (weeks 2 and 8) and monocyte chemo-attractant protein 1 (MCP-1) (week 2) levels were significantly decreased compared with baseline. In the ranibizumab group, placental growth factor (PIGF) (week 2) and vascular endothelial growth factor (VEGF) (week 2 and 8) levels were significantly decreased compared with baseline. No significant changes in central retinal thickness (CRT) or Early Treatment Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA) were observed in the Ozurdex group at any time-points. ETDRS scores significantly increased at week 20 (84.88 ± 8.88 letters) compared with baseline (74.78 ± 14.85 letters), and the CRT decreased significantly at week 4 (381.00 ± 114.64 µm) compared with baseline (440 ± 144 µm) in the Lucentis group. CONCLUSION: The dexamethasone implant affected the aqueous cytokines and proteins MCP-1, sICAM-1, sVCAM-1 and MIG, whereas ranibizumab treatments reduced VEGF and PIGF levels. Morphological changes may diverge from cytokine changes. Results may indicate a rationale for a combination therapy for CSME using both agents, the dexamethasone implant and repeatedly administered ranibizumab injections.

Intrathoracic complications associated with trans-femoral transcatheter aortic valve replacement: Implications for emergency surgical preparedness.

BACKGROUND: Intrathoracic complications (ITC) requiring emergency surgical intervention occur during transcatheter aortic valve replacement (TAVR). OBJECTIVES: Characterize the incidence, outcomes and predictors of ITC in a large cohort of transfemoral (TF) TAVR cases over a 5 year period. METHODS: Retrospective registry and chart review of all nonclinical trial TF-TAVR patients from seven centers within one hospital system from 2012-2016. ITC were defined as cardiac perforation, new or worsening pericardial effusion/tamponade, annular rupture, thoracic aortic injury, aortic valve dislodgement, and coronary artery occlusion. Procedural and 30-day outcomes and 1-year mortality were compared between ITC and no ITC patients. Multivariable logistic regression was used to identify predictors of ITC. RESULTS: Over the study period, 1,581 patients had TF-TAVR and 68 ITC occurred in 46 patients (2.9%). The most common ITCs were pericardial effusion/tamponade (59%), cardiac perforation (33%), and valve dislodgement (33%). ITC rate did not decline over time (rate (95% confidence interval) for 2012 = 0% (0-8.8%), 2013 = 1.3% (0-7.2%), 2014 = 4.4% (2.2-8.0%), 2015 = 3.5% (2.0-5.6%), and 2016 = 2.4% (1.5-3.8%)). ITC patients had worse 1-year survival (ITC: 60.7% (45.1-73.1%), no ITC: 88.7% (87.0-90.3%); p < .001). The majority of ITC patient deaths occurred within the first 30 days. Multivariable models to predict ITC were not successful. CONCLUSIONS: ITC did not decline over time in our cohort. Predictors of ITC could not be identified. While these events are rare, they are associated with worse procedural outcomes and mortality. Heart teams should continue to be prepared for emergency intervention.

Differences in Optic Nerve Head Blood Flow Regulation in Normal Tension Glaucoma Patients and Healthy Controls as Assessed With Laser Speckle Flowgraphy During the Water Drinking Test.

PRéCIS:: Optic nerve head (ONH) perfusion was not significantly altered in subjects with normal tension glaucoma (NTG) nor in healthy individuals after performing the water drinking test (WDT), because of its limited effect on ocular perfusion pressure (OPP). PURPOSE: ONH blood flow can be maintained stable in healthy individuals because of a physiological phenomenon called autoregulation. Impairment of autoregulation has been shown especially under condition of NTG. The purpose of this study was to investigate the ONH blood flow autoregulation in patients with NTG by influencing the OPP with the WDT. METHODS: The study included 9 eyes from 9 white patients with a diagnosis of NTG and 9 eyes from age-matched and sex-matched healthy individuals. In the glaucoma group, the antiglaucomatous therapy was paused 3 weeks before the investigations. Measurements of ONH blood flow were performed with laser speckle flowgraphy. After baseline measurements, individuals ingested 800 mL of water in <5 minutes. Measurements were repeated after 15, 30, and 45 minutes. RESULTS: The water ingestion led to a significant rise in intraocular pressure (P<0.001) but also mean arterial pressure (P<0.001) in both groups. This resulted in stable OPP (P=0.051) with no significant difference between the groups (P=0.43). ONH blood flow remained stable over time in both groups (P=0.719). No significant interaction of time and group was shown for all parameters. CONCLUSIONS: Our findings show that the WDT does not significantly influence the OPP and therefore has to be considered inferior to other methods used to assess blood flow autoregulation.

Short-term effect on the ocular circulation induced by unilateral intravitreal injection of aflibercept in age-related maculopathy.

PURPOSE: Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the standard treatment for neovascular age-related macular degeneration (AMD). As VEGF is a physiological key player for regulating retinal vascular tone, questions have been raised whether the application of anti-VEGF could induce alterations in ocular perfusion. METHODS: The study included 20 eyes from 20 Caucasian patients with unilateral neovascular AMD and 20 fellow eyes. All eyes were treated with standard intravitreal injection of aflibercept (IVA). Measurements of blood flow at the optic nerve head (ONH) and the choroid were performed with laser speckle flowgraphy (LSFG). The intraocular pressure (IOP), systolic and diastolic blood pressure, heart rate, mean arterial pressure (MAP) and ocular perfusion pressure (OPP) were analysed. Measurements were performed at baseline and repeated immediately after the injection and 30 and 45 min later. RESULTS: Mean time between injection of aflibercept and first follow-up was 8:56 ± 4:25 min. The injection led to significant rise in IOP. In the injected eyes, mean blur rate (MBR, i.e. a relative measure of perfusion and the main outcome parameter of LSFG) within the major vessels of the ONH as well as at the entire ONH region decreased significantly (p < 0.001). No change in MBR was observed in the fellow eye. Choroidal blood flow was maintained stable in both eyes. CONCLUSION: Intravitreal injection of aflibercept (IVA) led to a short-term reduction in perfusion only in the treated eye. This was independent from IOP, indicating a direct pharmacological effect. No changes in choroidal perfusion were observed during the first 45 min after the injection.

Laser speckle flowgraphy derived characteristics of optic nerve head perfusion in normal tension glaucoma and healthy individuals: a Pilot study.

The purpose of this prospective, case control study was to investigate the differences in optic nerve head blood flow measured with Laser Speckle Flowgraphy (LSFG) between Caucasian patients with normal tension glaucoma and healthy subjects. It included 20 eyes from 20 Caucasian patients with diagnosis of normal tension glaucoma and 20 eyes from age- and sex-matched healthy individuals. In the glaucoma group the antiglaucomatous therapy was paused 3 weeks prior to the investigations. Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate was obtained for different vascular compartments of the optic nerve head. Parameters for the characterization of pulse-waveform of the mean blur rate were calculated. It was shown that the mean blur rate was significantly lower in the glaucoma group compared to the control group (P < 0.001). The significant differences in the pulse-waveform parameters blow out time (P = 0.028) and flow acceleration time index (P < 0.001) indicate a flatter curve in NTG patients. In conclusion, LSFG can detect differences in optic nerve head blood flow between eyes with normal tension glaucoma and healthy eyes.

Stromal remodeling and lenticule thickness accuracy in small-incision lenticule extraction: One-year results.

PURPOSE: To prospectively characterize the stromal thickness changes during the first year after myopic small-incision lenticule extraction using spectral-domain optical coherence tomography (SD-OCT). SETTING: Department of Ophthalmology, Kepler University Hospital, Linz, Austria. DESIGN: Prospective case series. METHODS: This study evaluated eyes that had small-incision lenticule extraction to treat myopia or myopic astigmatism. A high-resolution SD-OCT system (RS 3000 Advance) in conjunction with a custom image-segmentation algorithm was applied to directly measure stromal thickness within the central 5.0 mm corneal zone. Measurements were obtained preoperatively and postoperatively at 1 day, 1 week, 6 weeks, 3 months, 6 months, and 1 year. RESULTS: The study enrolled 42 eyes of 21 patients. The mean surgical refractive correction was -4.94 diopters ± 1.75 (SD). Postoperatively, the stromal thickness showed a significant decrease during the first 6 weeks, which amounted to a mean of 10.4 ± 6.3 µm at the apex (P < .001). Subsequently, the central stroma thickened by a mean of 8.8 ± 5.9 µm up until the 1-year follow-up (P < .001). One year postoperatively, the mean observed central stromal thickness reduction was 18.7 ± 5.7 µm smaller than the planned lenticule thickness. This difference was smallest 6 weeks postoperatively (mean 9.8 ± 7.8 µm). CONCLUSIONS: Significant anatomic changes in the corneal stroma were detected during the first year after small-incision lenticule extraction. The achieved lenticule thickness was systematically lower than planned, and the mismatch was more pronounced with higher lenticule thickness. Refractive outcomes did not appear to be influenced by lenticule thickness accuracy.

Intraindividual comparison between femtosecond laser-assisted and conventional cataract surgery.

PURPOSE: To compare the safety and efficacy between femtosecond laser-assisted cataract surgery using the Victus laser system and conventional cataract surgery. SETTING: Department of Ophthalmology, Kepler University Hospital, Linz, Austria. DESIGN: Prospective randomized case series. METHODS: Both eyes of patients with age-related cataract were randomized to conventional cataract surgery or femtosecond laser-assisted cataract surgery, both with intraocular lens (IOL) implantation. Postoperative follow-up was at 1 day, 1 week, 1 month, 3 months, and 6 months and comprised corrected distance visual acuity, endothelial cell density (ECD), central corneal thickness (CCT), and central retinal thickness. The main outcomes were intraoperative and postoperative complications and the effective phacoemulsification time (EPT). Intraocular lens and capsulotomy centration were evaluated using retroillumination slitlamp photography. RESULTS: The study enrolled 50 patients. No intraoperative complications occurred in either group. The ECD, CCT, and central retinal thickness were similar between the groups at all follow-up examinations (P > .05). The EPT was not statistically significantly different between the groups (P = .22). The IOL centration was similar between the groups (P = .93). CONCLUSION: Femtosecond laser-assisted and conventional cataract surgery using the mentioned system were equally safe and effective.

Corneal Epithelial Remodeling Induced by Small Incision Lenticule Extraction (SMILE).

PURPOSE: To assess the reactive changes of the corneal epithelial thickness (ET) profile induced by small incision lenticule extraction (SMILE) for treatment of myopia. METHODS: This prospective observational study included 46 eyes of 23 patients that were scheduled for myopic SMILE. High-resolution spectral-domain optical coherence tomography (SD-OCT) and a custom image segmentation algorithm were applied to measure corneal ET at multiple time points within the central 5-mm zone. Postoperative ET alterations were correlated with treatment parameters and refractive outcomes. RESULTS: Mean age was 33 ± 6 years and mean spherical equivalent of surgical refractive correction was -4.78 ± 1.75 diopters. The average ET (averaged over the central 5-mm zone) increased from 52.3 ± 3.6 µm preoperatively to 57.7 ± 5.1 µm 6 months postoperatively (P < 0.01). Average ET was 101.9% of the preoperative thickness at 24 hours postoperatively, 103.2% at 1 week, 106.7% at 6 weeks, 109.3% at 3 months, and 110.4% at 6 months postoperatively. The epithelial thickening response could be modeled by an exponential recovery function and stabilized after 3 months. The extent of epithelial hyperplasia was highly dependent on the magnitude of the induced refractive correction (P = 0.002). CONCLUSIONS: In this initial study of corneal ET remodeling after myopic SMILE, significant epithelial thickening was detected as a function of the extent of surgical refractive correction. Moreover, the epithelial remodeling response to the corneal refractive change appeared to decrease with higher age. In our hands, the observed epithelial changes did not appear to affect the refractive outcome of SMILE. (ClinicalTrials.gov number, NCT02614625).

Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency.

PURPOSE: Mutations in the coding sequence of the L and M opsin genes are often associated with X-linked cone dysfunction (such as Bornholm Eye Disease, BED), though the exact color vision phenotype associated with these disorders is variable. We examined individuals with L/M opsin gene mutations to clarify the link between color vision deficiency and cone dysfunction. METHODS: We recruited 17 males for imaging. The thickness and integrity of the photoreceptor layers were evaluated using spectral-domain optical coherence tomography. Cone density was measured using high-resolution images of the cone mosaic obtained with adaptive optics scanning light ophthalmoscopy. The L/M opsin gene array was characterized in 16 subjects, including at least one subject from each family. RESULTS: There were six subjects with the LVAVA haplotype encoded by exon 3, seven with LIAVA, two with the Cys203Arg mutation encoded by exon 4, and two with a novel insertion in exon 2. Foveal cone structure and retinal thickness was disrupted to a variable degree, even among related individuals with the same L/M array. CONCLUSIONS: Our findings provide a direct link between disruption of the cone mosaic and L/M opsin variants. We hypothesize that, in addition to large phenotypic differences between different L/M opsin variants, the ratio of expression of first versus downstream genes in the L/M array contributes to phenotypic diversity. While the L/M opsin mutations underlie the cone dysfunction in all of the subjects tested, the color vision defect can be caused either by the same mutation or a gene rearrangement at the same locus.

Semiautomated SD-OCT Measurements of Corneal Sublayer Thickness in Normal and Post-SMILE Eyes.

PURPOSE: To test the reliability of a novel algorithm for measuring corneal epithelial thickness (ET) and stromal thickness of normal eyes and post-small incision lenticule extraction (SMILE) corneas with spectral-domain optical coherence tomography. METHODS: In this prospective observational study, a customized semiautomated software algorithm was developed and applied to measure corneal ET and stromal thickness along the horizontal corneal meridian. Measurements were performed by 2 examiners in a randomized fashion on a sample of 40 eyes with previous SMILE for treatment of myopia and a control group composed of 40 normal eyes. The intrauser repeatability and interuser reproducibility were analyzed by calculating typical indices including the coefficient of variation and intraclass correlation coefficient. Corneal sublayer thickness profiles were compared between normal and post-SMILE eyes. RESULTS: In both groups, coefficients of variation were 3.2% or lower and intraclass correlation coefficients were 0.929 or higher indicating excellent reliability of the measurement method. Central ET was on an average 6 µm greater in post-SMILE corneas (58.8 ± 5.4 µm) compared with normal eyes (52.8 ± 4.0 µm), with P < 0.01. Also, there was greater interindividual variability in ET in post-SMILE corneas and their horizontal epithelial profile seemed to show a lenticular appearance. CONCLUSIONS: Highly favorable indices of measurement reliability were achieved for this novel method of measuring corneal sublayer pachymetry not only in normal eyes but also in eyes with previous SMILE. The corneal ET profile was significantly altered in post-SMILE eyes compared with normal corneas.

Effect of Leptin Administration on Circulating Apolipoprotein CIII levels in Patients With Lipodystrophy.

CONTEXT: Apolipoprotein CIII (apoCIII), an inhibitor of lipoprotein lipase, plays an important role in triglyceride metabolism. However, the role of apoCIII in hypertriglyceridemia in lipodystrophy and the effects of leptin replacement on apoCIII levels are unknown. OBJECTIVE: The objective of the study was to test the hypotheses that apoCIII is elevated in hypertriglyceridemic patients with lipodystrophy and that leptin replacement in these patients lowers circulating apoCIII. DESIGN, SETTING, STUDY PARTICIPANTS, INTERVENTION, AND OUTCOME MEASURES: Using a post hoc cross-sectional case-control design, we compared serum apoCIII levels from patients with lipodystrophy not associated with HIV (n = 60) and age-, gender-, race-, and ethnicity-matched controls (n = 54) participating in ongoing studies at the National Institutes of Health. In a prospective, open-label, ongoing study, we studied the effects of 6­12 months of leptin replacement on apoCIII in lipodystrophy patients as an exploratory outcome. RESULTS: ApoCIII was higher in lipodystrophy patients (geometric mean [25th and 75th percentiles]) (23.9 mg/dL [14.6, 40.3]) compared with controls (14.9 mg/dL [12.3, 17.7]) (P < .0001). ApoCIII and triglyceride levels were positively correlated in patients with lipodystrophy (R = 0.72, P < .0001) and healthy controls (R = 0.6, P < .0001). Leptin replacement (6­12 mo) did not significantly alter apoCIII (before leptin: 23.4 mg/dL [14.5, 40.1]; after leptin: 21.4 mg/dL [16.7, 28.3]; P = .34). CONCLUSIONS: Leptin replacement in lipodystrophy did not alter serum apoCIII levels. Elevated apoCIII may play a role in the hypertriglyceridemia of lipodystrophy independent of leptin deficiency and replacement.