The Effectiveness and Safety of a Novel Crosslinked Hyaluronate Canalicular Gel Occlusive Device for Dry Eye.

PURPOSE: Evaluate effectiveness and safety of a crosslinked hyaluronate (HA) canalicular filler (Lacrifill Canalicular Gel) compared to a commercially available hydrogel canalicular plug (Form Fit). SETTING: 5 sites in United States. DESIGN: Prospective, multicenter, controlled, double-masked, randomized 2:1 (filler:plug). METHODS: Adults (≥22 years) with Schirmer test (with anesthesia) ≤10 mm/5 minutes, presence of corneal staining, ocular surface disease index (OSDI) of ≥23 with ≤3 responses of "not applicable," patent lacrimal drainage system, and bilateral best-corrected distance visual acuity of 20/40 or better. Filler or plugs were instilled bilaterally in the inferior canaliculi. Primary effectiveness endpoint was non-inferiority of the mean within subject change from baseline to Month 3 in Schirmer score for patients receiving filler compared to plugs. The key secondary effectiveness endpoint was non-inferiority of the proportion of patients with filler achieving improvement from baseline to Month 3 in OSDI by a minimal clinically important difference (MCID). Additional endpoints included the mean change from baseline to 3 and 6 months in tear meniscus height, OSDI, corneal staining, tear break-up time, and safety. RESULTS: 157 patients were randomized; 99 patients with crosslinked HA filler and 52 patients with hydrogel plugs completed the study. Filler was non-inferior to plugs in the mean Schirmer score change from baseline and in the proportion of patients achieving a clinically important improvement in OSDI. CONCLUSIONS: Crosslinked HA filler is a safe, well-tolerated, and effective method to treat dry eye. Clinically and statistically significant improvements in signs and symptoms of dry eye were sustained through 6 months.

Safety and effectiveness comparison of a new cohesive ophthalmic viscosurgical device.

PURPOSE: To evaluate the safety and effectiveness of a new cohesive ophthalmic viscosurgical device (OVD) (StableVisc) compared with a marketed cohesive OVD (ProVisc) in patients undergoing cataract surgery. SETTING: 22 sites in the United States. DESIGN: Prospective multicenter controlled double-masked and randomized 1:1 (StableVisc:ProVisc; stratified by site, age group, and cataract severity). METHODS: Adults (≥45 years) with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens implantation were included. Patients were randomized to receive either StableVisc or ProVisc during standard cataract surgery. Postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety endpoint was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority between the devices was tested. Inflammation and adverse events were evaluated. RESULTS: 390 patients were randomized; 187 patients with StableVisc and 193 patients with ProVisc completed the study. StableVisc was noninferior to ProVisc in mean ECD loss from baseline to 3 months (17.5% and 16.9%, respectively). StableVisc was noninferior to ProVisc in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (5.2% and 8.2%, respectively). CONCLUSIONS: The StableVisc cohesive OVD, which provides both mechanical and chemical protection, was safe and effective when used in cataract surgery and provides surgeons with a new cohesive OVD.

The EVO ICL for Moderate Myopia: Results from the US FDA Clinical Trial.

Purpose: To evaluate the safety and effectiveness of collamer posterior chamber phakic refractive lenses with a central port design (EVO and EVO+ Sphere and Toric implantable collamer lenses [ICLs]) for correction of moderate myopia with or without astigmatism. Patients and Methods: Six-month results of a multicenter clinical trial were performed under United States FDA Investigational Device Exemption. Subjects 21 through 45 years of age with manifest refraction spherical equivalent ranging from -3.00 D to -6.00 D and astigmatism up to 4.00 D underwent implantation of EVO or EVO+ Sphere or Toric ICLs. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, intraocular pressure (IOP), endothelial cell density, and adverse events were evaluated over 6 months. Results: This report includes a retrospective review of 200 eyes of 114 subjects with mean age 35.1 ± 5.1 years that completed the 6-month visit. Mean preoperative spherical equivalent (SE) measured -4.61 ± 0.87 D (range: -3.00 to -6.00 D). At 6 months, mean SE was -0.085 ± 0.26 D, with 91.5% within ± 0.50 D of target and 100.0% within ±1.00 D of target. Mean postoperative UDVA and CDVA were -0.065 ± 0.08 logMAR and -0.14 ± 0.07 logMAR, respectively. About 98.0% of eyes maintained or gained lines of CDVA, and no eye lost more than 1 line CDVA. Efficacy and safety indices were 1.03 and 1.21, respectively. No eye experienced pupillary block, required preoperative or postoperative peripheral iridotomy or iridectomy, developed anterior subcapsular cataract or had elevated IOP due to angle narrowing or pigment dispersion. Mean endothelial cell density declined by 2.2%. Conclusion: EVO ICL lenses demonstrated accuracy, predictability and stability of refractive correction with achievement of high levels of UDVA and an excellent safety profile for patients with moderate myopia with or without astigmatism.

Efficacy of a One-Piece Aberration Neutral Hydrophobic Acrylic Toric Intraocular Lens.

Purpose: To assess the refractive outcomes, intraocular centration and rotational stability of the enVista toric intraocular lens (IOL). Patients and Methods: This study was a prospective, multi-centre, double-masked, partially randomized and partially controlled clinical trial. A total of 191 participants were implanted with toric IOL (1.25, 2.00, or 2.75D) or non-toric IOL (control). The lowest range of corneal astigmatic eyes were randomized to 1.25D toric or control. Higher astigmatic powers were allocated to the treatment arm. Subjects were assessed immediately postoperatively, 1-2 (V1), 7-14 (V2), 30-60 (V3) and 120-180 (V4) days postoperatively. Unaided (UDVA) and distance corrected visual acuity (CDVA), manifest refraction and corneal curvature were assessed. Vector analysis was used to calculate surgically induced refractive correction (SIRC), correction ratio (CR), error magnitude (EM) and error vector (EV). Slit-lamp photography was used to measure centration and rotational stability. Results: UDVA was better in the low toric IOL group in comparison with the control group at V4 (p<0.001). There was an undercorrection in the control group, whereas the average CR for all toric subjects was 1.00 ± 0.32: V2, 0.98 ± 0.34: V3 and 0.98 ± 0.35: V4. The absolute IOL rotational stability in comparison to the position of the IOL at V1 was 1.35° ± 0.97°: V2, 1.35° ± 1.07°: V3 and 1.38° ± 1.25°: V4. Decentration was generally inferior (V1: 0.04 ± 0.22mm, V2: 0.05± 0.20mm, V3: 0.08 ± 0.22mm, V4: 0.04 ± 0.21mm) and nasal (V1: 0.19 ± 0.23mm, V2: 0.20 ± 0.20mm, V3: 0.20 ± 0.21mm, V4: 0.17 ± 0.22mm). Conclusion: Participants with low levels of corneal astigmatism achieved superior vision and refractive outcomes in the low toric group over the control. Moderate and high levels of astigmatism achieved excellent refractive outcomes. The toric IOL demonstrated high levels of both rotational and centrational stability.

Evaluation of the EVO/EVO+ Sphere and Toric Visian ICL: Six Month Results from the United States Food and Drug Administration Clinical Trial.

Purpose: To evaluate the safety and effectiveness of Collamer posterior chamber phakic refractive lenses with a central port design (EVO and EVO+ Sphere and Toric Visian ICLs) for correction of moderate-to-high myopia with or without astigmatism. Patients and Methods: Six-month results of a multicenter clinical trial performed under United States FDA Investigational Device Exemption. Subjects 21 through 45 years of age with myopia ranging from -3.00 D to -20.00 D and astigmatism up to 4.00 D underwent implantation of EVO or EVO+ Sphere or Toric Visian ICLs. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, intraocular pressure (IOP), endothelial cell density, and adverse events were evaluated over 6 months. Results: This clinical trial enrolled 629 eyes of 327 subjects with mean age 35.6 ± 5.09 years. Mean preoperative spherical equivalent (SE) measured -7.62 ± 2.75 D (range: -3.00 to -15.62 D). At 6 months, mean SE was -0.079 ± 0.33 D, with 90.5% within ± 0.50 D of target and 98.9% within ±1.00 D of target. Mean postoperative UDVA and CDVA were -0.059 ± 0.10 logMAR and -0.13 ± 0.08 logMAR, respectively. 52.3% of eyes gained lines of CDVA. Efficacy and safety indices were 1.06 and 1.24, respectively. No eye experienced pupillary block, required peripheral iridotomy or iridectomy, developed anterior subcapsular cataract or had elevated IOP due to angle narrowing or pigment dispersion. Mean endothelial cell density declined by 2.3%. Conclusion: EVO ICL lenses demonstrated accuracy of refractive correction and achievement of high levels of UDVA. This clinical trial confirmed that the central port design of EVO and EVO+ Sphere and Toric Visian ICL lenses functions effectively to allow physiologic flow of aqueous humor, thus eliminating the requirement for preoperative peripheral iridotomies. The results of this clinical trial resulted in FDA approval on March 25, 2022.

Safety and effectiveness of a new ophthalmic viscosurgical device: randomized, controlled study.

PURPOSE: To evaluate the safety and effectiveness of a new dispersive ophthalmic viscosurgical device (OVD) (ClearVisc) compared with an approved dispersive OVD (Viscoat) when used in cataract surgery. SETTING: 16 clinics in the United States. DESIGN: Prospective multicenter controlled randomized 1:1 (ClearVisc:Viscoat; stratified by site, age group, and cataract severity). Patients and examiners masked. METHODS: Patients aged 45 years or older with age-related noncomplicated cataract considered amenable to treatment with standard phacoemulsification cataract extraction and intraocular lens (IOL) implantation were included. Patients were randomized to receive either ClearVisc or Viscoat using standard techniques. 5 postoperative visits occurred at 6 hours, 24 hours, 7 days, 1 month, and 3 months. The primary effectiveness outcome was the change in endothelial cell density (ECD) from baseline to 3 months. The primary safety end point was the proportion of patients who experienced at least 1 intraocular pressure (IOP) measurement ≥30 mm Hg at any follow-up visit. Noninferiority was tested. Inflammation and adverse events were evaluated. RESULTS: 372 patients were randomized: 184 patients in the ClearVisc group and 188 patients in the Viscoat group. ClearVisc was noninferior to Viscoat in mean percentage of ECD loss from baseline to 3 months (8.4% and 6.8%, respectively). ClearVisc was significantly noninferior to Viscoat in the proportion of patients with postoperative IOP ≥30 mm Hg at any follow-up visit (17.4% and 20.3%, respectively, P = .0002). CONCLUSIONS: ClearVisc dispersive OVD provides surgeons with a new option in the continuum of approved dispersive OVDs with beneficial properties as a surgical aid in cataract extraction and IOL implantation.

Accuracy and safety of partial thickness femtosecond laser radial and arcuate keratotomy incisions in porcine eyes.

BACKGROUND: To evaluate the accuracy and safety of micro radial and arcuate keratotomy incisions constructed by a femtosecond laser system with a curved contact patient interface in porcine eyes. METHODS: Partial thickness micro radial and arcuate keratotomy incisions were constructed in porcine eyes with a femtosecond laser system and evaluated for precision of depth, quality, and consistency. Optical coherence tomography was used to determine the accuracy and precision of incision depth. Corneal endothelial safety was assessed by a fluorescent live/dead cell viability assay to demonstrate laser-induced endothelial cell loss. Quality was evaluated by ease of opening and examination of interfaces. RESULTS: In two micro radial incision groups, intended incision depths of 50% and 80% resulted in mean achieved depths of 50.01% and 77.69%, respectively. In three arcuate incision groups, intended incision depths of 80%, 600 µm or 100 µm residual uncut bed thickness resulted in mean achieved depths of 80.16%, 603.03 µm and residual bed of 115 µm, respectively. No loss of endothelial cell density occurred when the residual corneal bed was maintained at a minimum of 85-116 µm. The incisions were easy to open, and interfaces were smooth. CONCLUSIONS: A femtosecond laser system with curved contact interface created precise and reproducible micro radial and arcuate keratotomy incisions. Accuracy and precision of the incision depth and preservation of endothelial cell density demonstrated the effectiveness and safety of the system.

Performance and Safety of the Extended Depth of Focus Implantable Collamer® Lens (EDOF ICL) in Phakic Subjects with Presbyopia.

PURPOSE: To evaluate the performance and safety of the Extended Depth of Focus Implantable Collamer® Lens (EDOF ICL) for improvement of uncorrected near, intermediate and distance visual acuity in phakic subjects with myopia and presbyopia. DESIGN: Prospective multicenter study. METHODS: Presbyopic subjects who required an EDOF ICL in the range of -0.50 D to -18.00 D, exhibited ≤ 0.75 D refractive astigmatism and required from +1.00 to +2.50 D reading add were implanted bilaterally. Assessments at 6 months included uncorrected near, intermediate and distance visual acuities, defocus curves, contrast sensitivity, responses to the National Eye Institute Refractive Error Quality of Life Questionnaire and a Task Assessment Questionnaire. RESULTS: A total of 34 subjects completed the study. Investigators targeted emmetropia in all eyes. Mean binocular uncorrected near, intermediate and distance visual acuities measured logMAR -0.01 ± 0.05 (20/20), -0.02 ± 0.08 (20/19) and 0.07 ± 0.10 (20/23), respectively. Mean monocular uncorrected near, intermediate and distance visual acuities measured logMAR 0.068 ± 0.09 (20/23), 0.062 ± 0.10 (20/23) and 0.16 ± 0.12 (20/29). There were no clinically or statistically significant differences in contrast sensitivity between baseline and 6 months under any testing conditions. Subjects reported significant improvements in measures of vision-related quality of life and ability to perform tasks at all distances without glasses or contact lenses. Overall, satisfaction with the EDOF ICL was high: postoperatively, 91.2% of subjects were satisfied with their vision. CONCLUSION: This multicenter, prospective clinical investigation demonstrated the ability of the EDOF ICL to correct myopia and presbyopia, resulting in improvement of uncorrected near, intermediate and distance visual acuity without compromising the quality of vision. The EDOF ICL allowed subjects to perform tasks of daily living without glasses or contact lenses. Subjects reported significant improvements in quality of life with high levels of spectacle independence and satisfaction.

Femtosecond laser-assisted arcuate keratotomy at the time of cataract surgery for the management of preexisting astigmatism.

PURPOSE: To evaluate the outcomes of femtosecond laser-assisted arcuate keratotomy combined with cataract surgery in eyes with low-to-moderate corneal astigmatism. SETTING: Eyes of York Private Practice Ophthalmology Clinic, York, Pennsylvania, USA. DESIGN: Retrospective case series. METHODS: This retrospective analysis included case records of patients with preexisting corneal astigmatism ranging from 0.5 to 2.0 diopter (D). Study parameters included corneal astigmatism, refractive astigmatism, and uncorrected (UDVA) and corrected (CDVA) distance visual acuities. The results, which were analyzed at 3 months postoperatively, included frequency distribution histograms, vector analysis, and single-angle polar plots. RESULTS: The study comprised case records of 189 eyes of 143 patients (56 men and 87 women). The postoperative refractive astigmatism was reduced significantly compared with preoperative corneal astigmatism to 0.14 D ± 0.23 (SD) from 0.92 ± 0.34 D (P < .001). One hundred eighty-one eyes (95.8%) demonstrated postoperative refractive astigmatism of 0.5 D or less. The mean surgically induced change along the preoperative steep axis was -0.59 ± 0.56 D, and the change along the orthogonal axis was 0.01 ± 0.35 D. Postoperatively, 171 eyes (90.5%) had astigmatism angle of error of 15 degrees or less. The postoperative mean UDVA and CDVA were 0.09 ± 0.16 logarithm of the minimum angle of resolution (logMAR) and 0.02 ± 0.05 logMAR, respectively. One hundred seventy eyes (90%) had a postoperative UDVA of 20/30 or better. The results demonstrated stability at 12 months postoperatively. No intraoperative or postoperative arcuate keratotomy-related events were observed. CONCLUSION: The results suggest that femtosecond laser-assisted arcuate keratotomy represents a safe and effective method for astigmatism correction at the time of cataract surgery with demonstrated stability of correction for at least 1 year postoperatively.

Femtosecond laser-assisted capsulotomy with capsular marks for toric IOL alignment: Comparison of tensile strength with standard femtosecond laser capsulotomy.

PURPOSE: To compare the capsulotomy rim strength with capsular marks (CMs) to the rim strength without CMs in porcine eyes, and to demonstrate the practicality of CMs for intraoperative toric intraocular lens (IOL) alignment. SETTING: LENSAR facility, Orlando, Florida, USA. DESIGN: Laboratory study. METHODS: The biomechanical strength of the capsulotomy with CMs was tested under two different load orientations (orthogonal to or in-line with CMs). Thirty-six porcine eyes were randomly assigned to three treatment cohorts: (1) standard capsulotomy with no CMs, (2) capsulotomy with CMs for in-line tensile testing and (3) capsulotomy with CMs for orthogonal tensile testing. Study parameters were capsulotomy break force and maximum extensibility. The ease of using CMs for toric IOL alignment was also evaluated. RESULTS: There was no significant difference between the mean break force for standard capsulotomy (180.57 mN ± 22 [SD]), capsulotomy with CMs with orthogonal load (178.04 ± 20 mN, P = 1.000), and with in-line load (181.05 ± 15 mN, P = 1.000). Likewise, the mean extensibility at the break point for standard capsulotomy (6.47 ± 0.33 mm) was equivalent to the mean extensibility with CMs with orthogonal load (6.49 ± 0.45 mm, P = 1.000) and with in-line load (6.3 ± 0.47 mm, P = .960). In the implanted eyes, toric IOLs were found to be easily aligned with the CMs. CONCLUSION: The femtosecond laser capsulotomies with CMs were equivalent in tensile strength and extensibility to standard femtosecond laser capsulotomies and showed high potential for effective alignment of toric IOLs.

The Implantable Collamer Lens with a central port: review of the literature.

The purpose of this review is to summarize preclinical and clinical data from publications appearing in the peer-reviewed scientific literature relevant to the safety and effectiveness of the EVO Implantable Collamer Lens (ICL) posterior chamber phakic refractive lens with a central port (V4c Visian ICL with KS Aquaport, STAAR Surgical, Inc.). A literature search was conducted using PubMed.gov to identify all articles relating to the EVO ICL. Articles were examined for their relevance, and the references cited in each article were also searched for additional relevant publications. On the basis of a total of 67 preclinical studies and clinical reports, including effectiveness data on 1,905 eyes with average weighted follow-up of 12.5 months and safety data on 4,196 eyes with weighted average follow up of 14.0 months, the EVO ICL is safe and effective for the correction of a broad range of refractive errors. High levels of postoperative uncorrected visual acuity, refractive predictability, and stability demonstrate the effectiveness of the EVO ICL. Safety data suggest reduced rates of anterior subcapsular cataract and pupillary block compared with earlier models. Improved safety and proven effectiveness make EVO an attractive option for surgeons and patients.

A review of the outcome of dental implant provision in individuals with movement disorders.

Movement disorders encompass a wide range of medical conditions that demonstrate changes to muscle function and tone which present with orofacial dyskinesia and dystonia. The most common conditions exhibiting these features are Parkinson's disease, Down syndrome, chorea and epilepsy. AIM: To establish whether implant success in patients suffering from movement disorders is similar to the general population, identifying risk factors and noting recommendations that may aid maintenance programmes. METHOD: PubMed and Medline searches, combined with a manual search of the reference lists of identified full text studies. In total, 19 patient case reports and 11 patient case series were identified for inclusion in the review. RESULTS: Implant survival in patients may be less than expected in patients with movement disorders, but evidence points to early rather than late failures. Oral hygiene control was widely reported as an issue, although there was insufficient evidence to imply that a lack of oral care will cause more rapid deterioration in implant patients with movement disorders. Maintenance requirements were low for fixed restorations, but more frequently reported in patients treated with overdentures, with the attachment mechanism and the prostheses requiring replacement. Chewing and quality of life in relation to prosthesis wear were improved. CONCLUSION: Provision of implant-supported prostheses improves chewing and quality of life for patients with movement disorders and should be considered as an option in the treatment planning for tooth loss in this group of patients. However, straightforward designs that lend themselves to easier long-term maintenance should be adopted.

Prospective multicenter clinical trial to evaluate the safety and effectiveness of a new glistening-free one-piece acrylic toric intraocular lens.

PURPOSE: Glistening formation in the intraocular lens (IOL) optic has the potential to impact quality of vision. The enVista One-Piece Hydrophobic Acrylic Spherical IOL Model MX60 (MX60 IOL) is currently the only US Food and Drug Administration-approved IOL with a label of "no glistenings". The purpose of this prospective, multicenter, partially randomized, partially controlled, double-masked, pivotal study was to evaluate the safety and effectiveness of the enVista One-Piece Hydrophobic Acrylic MX60T Toric IOL (enVista MX60T Toric IOL). PATIENTS AND METHODS: Subjects (n=191) were implanted with the enVista MX60T Toric IOL (cylinder powers 1.25, 2.00, or 2.75 D) or the parent MX60 IOL (control). Eyes within the lowest range of corneal astigmatism were randomized to receive either Toric 1.25 D IOL or control IOL in a 1:1 ratio. All subjects with corneal astigmatism requiring 2.00 or 2.75 D cylinder IOLs received toric IOLs. Rotational stability, cylinder reduction, and best-corrected distance visual acuity were primary effectiveness endpoints measured at Visit 4 (120-180 days postoperatively). RESULTS: Visit 4 mean absolute axis misalignment in the All Toric group was 4.68°±7.33°, and all subjects had ≤5° absolute rotation from Visit 3 to Visit 4. The 1.25 D group had significantly greater improvement in dioptric cylinder reduction (P<0.001), percent cylinder reduction (P<0.001), and mean uncorrected distance visual acuity (P<0.001), compared to control at Visit 4. Most adverse events (AEs) were mild, with no serious AEs in the study eyes. The rates of cumulative AEs through Visit 4 were below International Organization for Standardization (ISO) standard 11979-7 AE rates. CONCLUSION: enVista MX60T Toric IOL is safe and effective for patients with preoperative corneal astigmatism undergoing IOL implantation.

Comparison of Wound Sealability Between Femtosecond Laser-Constructed and Manual Clear Corneal Incisions in Patients Undergoing Cataract Surgery: A Pilot Study.

PURPOSE: To compare the sealability of femtosecond laser-constructed and manual clear corneal incisions (CCIs) in patients undergoing cataract surgery. METHODS: This prospective, randomized study included 62 eyes of 62 patients with cataract grade 1 to 2 (LOCS scale). The patients were randomly assigned (1:1) for creation of either manual CCI (with a 2.4-mm keratome) or femtosecond laser-assisted CCI (LENSAR, Inc., Orlando, FL) (31 eyes in each group) before undergoing femtosecond laser-assisted cataract surgery. Wound sealability was assessed as grade 1, 2, or 3 (1: need to reform anterior chamber and hydrate wound at end of surgery; 2: need to reform anterior chamber only; 3: formed anterior chamber, no hydration or anterior chamber reformation necessary). RESULTS: The nuclear sclerosis grade, cumulative dissipated energy and phacoemulsification time were comparable between the two groups. No complications were experienced in any of the patients. The mean wound sealability for the femtosecond laser group (2.35 ± 0.84) was statistically significantly better in comparison to the manual group (1.32 ± 0.65) (P < .001). At the end of the surgery, 22.6% (n = 7) of eyes in the femtosecond laser group needed reformation of the anterior chamber and hydration of the wound compared to 77.4% (n = 24) of eyes in the manual group. Conversely, 58.1% (n = 18) of eyes in the femtosecond laser group compared to 9.7% (n = 3) of eyes in the manual group were observed to have a formed anterior chamber. CONCLUSIONS: Femtosecond laser-created CCIs had significantly better wound sealability compared to those created with a metal keratome. [J Refract Surg. 2017;33(11):744-748.].

The Biological Basis of Chronic Traumatic Encephalopathy following Blast Injury: A Literature Review.

The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury. It served to inform participants objectively and help focus meeting discussion on identifying knowledge gaps and priority research areas. CTE is described generally as a progressive neurodegenerative disorder affecting persons exposed to head injury. Affected individuals have been participants primarily in contact sports and military personnel, some of whom were exposed to blast. The symptomatology of CTE overlaps with Alzheimer's disease and includes neurological and cognitive deficits, psychiatric and behavioral problems, and dementia. There are no validated diagnostic criteria, and neuropathological evidence of CTE has come exclusively from autopsy examination of subjects with histories of exposure to head injury. The perivascular accumulation of hyperphosphorylated tau (p-tau) at the depths of cortical sulci is thought to be unique to CTE and has been proposed as a diagnostic requirement, although the contribution of p-tau and other reported pathologies to the development of clinical symptoms of CTE are unknown. The literature on CTE is limited and is focused predominantly on head injuries unrelated to blast exposure (e.g., football players and boxers). In addition, comparative analyses of clinical case reports has been challenging because of small case numbers, selection biases, methodological differences, and lack of matched controls, particularly for blast-exposed individuals. Consequently, the existing literature is not sufficient to determine whether the development of CTE is associated with head injury frequency (e.g., single vs. multiple exposures) or head injury type (e.g., impact, nonimpact, blast-related). Moreover, the incidence and prevalence of CTE in at-risk populations is unknown. Future research priorities should include identifying additional risk factors, pursuing population-based longitudinal studies, and developing the ability to detect and diagnose CTE in living persons using validated criteria.