Population-Based Evaluation of Total Protein in Cerebrospinal Fluid.

OBJECTIVES: To present a normal range of cerebrospinal fluid (CSF) protein levels in a community-based population and to evaluate factors that contribute to CSF protein level variability. PATIENTS AND METHODS: Samples of CSF protein were obtained from participants aged 32 to 95 years who underwent lumbar puncture (LP) between November 1, 2007, and October 1, 2017, as part of the Mayo Clinic Study of Aging, a longitudinal, population-based study of residents of Olmsted County, Minnesota. RESULTS: A total of 633 participants (58.1% male; 99.1% White; mean ± SD age, 70.9±11.6 years) underwent LP with recorded CSF protein level. Mean ± SD CSF protein level was 52.2±18.4 mg/dL (to convert to mg/L, multiply by 10), with a 95% reference interval of 24.0 to 93.4 mg/dL (range, 14.0-148.0 mg/dL). Spinal stenosis and arterial hypertension were associated with higher CSF protein levels on univariable analysis (P<.001). Increasing age, male sex, and diabetes were all independently associated with higher CSF protein levels on multivariable analysis (P<.001). In the 66 participants with repeated LPs within 2.5 years, the coefficient of repeatability was 26.1 mg/dL. Eleven participants (16.7%) had a CSF protein level difference of 20 mg/dL or more between serial LPs, and 4 (6.1%) had a difference of 25 mg/dL or more. There was a trend toward greater CSF protein level variability in patients with spinal stenosis (P=.054). CONCLUSION: This large population-based study showed that CSF protein level can vary significantly among individuals. Elevated CSF protein level was independently associated with older age, male sex, and diabetes and is higher than listed in many laboratories. These findings emphasize the necessity of evidence-based reevaluation and standardization of CSF protein metrics.

Comparing Surgical and Clinical Success Rates of Ahmed FP7, and Baerveldt 250 and Baerveldt 350 Glaucoma Drainage Devices.

PRCIS: Surgical and clinical success rates were similar among Ahmed FP7, and Baerveldt 250 and 350 glaucoma drainage devices at three years. PURPOSE: To compare rates of surgical and clinical success in patients with Ahmed FP7 (FP7), Baerveldt 250 (B250), or Baerveldt 350 (B350) glaucoma drainage devices (GDDs). DESIGN: A retrospective cohort study. METHODS: A total of 157 eyes of 129 adult patients with FP7, B250, B350 GDDs, and 190 eyes of 99 medically controlled glaucoma patients were enrolled at a tertiary care institution from August 2017 through July 2019. They were followed through April 2020. The main outcome measures included surgical and clinical failure. Surgical failure was defined as intraocular pressure (IOP) outside 5-21 mm Hg, IOP reduced <20% below baseline, additional glaucoma surgery, GDD removal, or no light perception. Eyes that did not meet their goal IOP ranges or required secondary glaucoma interventions were deemed clinical failures. RESULTS: A total of 43 (12.4%) FP7, 36 (10.4%) B250, 78 (22.5%) B350, and 190 (54.8%) medically treated control eyes were enrolled. By the postoperative year 3 visit, 10 (23.2%) FP7, 11 (30.6%) B250, and 32 (41.0%) B350 eyes had met a surgical failure criterion ( P =0.127). There were no significant differences in the numbers of eyes meeting their IOP target ranges ( P =0.510), and rates of secondary glaucoma surgeries ( P =0.270). Overall clinical success was attained among 83.3% FP7, 81.8% B250, and 68.0% B350 eyes ( P =0.447). CONCLUSIONS: The GDD groups were similar in their rates of success, based on both the surgical and clinical success definitions.

Goldmann and modified Goldmann tonometry measuring intraocular pressure changes in eyes which underwent myopic laser in situ Keratomileusis and photorefractive keratectomy.

PURPOSE: Compare intraocular pressure (IOP) measured by a standard Goldmann applanation tonometer prism (IOPg) and a modified correcting applanation tonometer surface Goldmann prism (IOPc) before and after laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). METHODS: Goldmann tonometry was analyzed in a retrospective, cross-sectional study, using both GAT and modified-GAT prisms pre-operatively and at the 3 month post-operative appointment on 120 eyes (64 patients) who received LASIK (n = 58) or PRK (n = 62). Demographics, central corneal thickness (CCT), manifest refraction and corneal curvature (CC) data was collected at each visit as well as surgical parameters, including maximum ablation depth. RESULTS: Mean paired IOP following LASIK decreased by - 3.28 ± 3.2 mmHg measured by IOPg and - 1.93 ± 3.3 mmHg by IOPc (p ≤ 0.0001). Mean paired IOP following PRK reduced by - 1.92 ± 3.6 mmHg measured by IOPg and - 1.06 ± 3.6 mmHg by IOPc (p ≤ 0.0001). Increased LASIK ablation depth and post-procedural change in CCT trended toward a statistically significant reduction in IOPg (p = 0.07,p = 0.12), but not IOPc (p = 0.18,p = 0.32). PRK ablation depth was not associated with a reduction in IOPg or IOPc. DISCUSSION: The modified Goldmann (IOPc) prism measured less of an IOP reduction following LASIK and PRK compared to the standard (IOPg) prism, and the IOP reduction with both prisms was associated with the degree of myopic correction. WHAT IS ALREADY KNOWN AND THE RESIDUAL QUERY: Corneal refractive surgery generally demonstrates significant postoperative Goldmann IOP reductions. Presumably, this is due to corneal biomechanical changes for which a newer method of Goldmann IOP measurement may be able to compensate. WHAT THIS STUDY ADDS: A modified, corneal conforming Goldmann prism demonstrates significantly less IOP reduction following myopic LASIK and PRK compared to the standard flat Goldmann prism. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: A newer, modified Goldmann prism may help detect glaucoma and OHT at an earlier stage in patients which have undergone LASIK or PRK. The findings corroborate predicted corneal biomechanical changes following the most common corneal refractive procedures.

iSTAT (Intraluminal Suture Transfixed and Titratable) technique for ligature-free Reversal of long-term drainage implant hypotony.

Purpose: To describe the iSTAT (Intraluminal Suture Transfixed and Titratable) technique, an improvement on prior tube occlusion methods, allowing for variable flow. Observations: A 76-year-old woman who underwent an uncomplicated glaucoma drainage device (GDD) placement for uncontrolled mixed mechanism glaucoma presented with hypotony 4 years post-operatively. The iSTAT technique was performed to adjust the flow in the GDD tube: a 4-0 polypropylene suture tip was blunted with a low-temperature cautery, creating a bulbed end that would occlude the tube. The suture was introduced into the tube bulb-first intracamerally, extending to the plate. If partial occlusion of the tube is desired, the suture can be secured in place by piercing the side wall of the tube tip with the distal end of the suture. After complete occlusion of the GDD tube with a large bulb, the patient had intraocular pressures (IOPs) > 40 mmHg on post-operative day 1, which remained in the 25-30 mmHg range 2-3 weeks post-operatively on maximally tolerated medications. Patient underwent a second revision with a smaller-bulbed stent (with a 3-0 polypropylene suture), which stabilized her IOP at 8 mmHg. Conclusion and Importance: The iSTAT technique allows for an ab interno revision, titration of flow, and stabilization of the stent in the wall of the tube. The ab interno approach precludes the need for conjunctival incisions, thus maintaining bleb integrity and permitting surgery under topical anesthesia. The intracameral stabilization of the stent in the tube allows for smaller bulbs to titrate the flow without external ligatures.

Health-related quality of life in Ahmed FP7, and Baerveldt 250 and 350 patients compared with medical controls.

PURPOSE: To compare health-related quality of life (HRQoL) in patients with Ahmed FP7 (FP7), Baerveldt 250 (B250) and Baerveldt 350 (B350) glaucoma drainage device (GDDs), and medically treated controls. METHODS: This was a prospective cohort study from August 2017 to July 2019. The NEI 25-Item Visual Function Questionnaire (VFQ-25), the Adult Strabismus-20 questionnaire (AS-20) and the Diplopia Questionnaire were conducted ≥30 days postoperatively in GDD patients, on enrolment for controls. Age, sex, treatment type, visual acuity, mean deviation and diplopia were evaluated for association with HRQoL RESULTS: Of the 128 GDD patients enrolled, 35 (27.3%) had FP7, 32 (25.0%) had B250 and 61 (47.7%) had B350. In univariate analysis, decreased HRQoL was associated with younger age (r2 range 0.042-0.071), diplopia (r2 range 0.039-0.119), GDD treatment (r2 range 0.023-0.103), lower visual acuity (r2 range 0.021-0.215) and worse mean deviation (r2 range 0.029-0.131). All GDD groups had lower HRQoL subscores than the controls. HRQoL scores were lower compared with controls among B350 patients for AS-20 Self-perception subscale, B250 and B350 for Reading and General Function subscales, and FP7 and B350 for VFQ-25 Visual Functioning subscale. There were no significant differences among the GDDs. CONCLUSIONS: Glaucoma patients with a younger age, diplopia, lower visual acuity, worse mean deviation or a GDD had lower HRQoL. Those with B350 had lower self-perception scores, consistent with previous reports in the literature. This subscale was not diminished in FP7 or B250, so the decreased self-perception scores may be due to greater visibility or awareness of the B350.

Orbital anatomy magnetic resonance imaging in diplopic versus non-diplopic patients after glaucoma drainage device placement.

PURPOSE: New-onset persistent diplopia has become a common complication after glaucoma drainage device (GDD) placement. Understanding the orbital anatomy of such patients may provide information regarding risk of diplopia, GDD selection, and post-operative management. The purpose of this study was to examine the orbital anatomic differences in diplopic and non-diplopic patients after GDD implantation using high-resolution MRI. METHODS: Seven eyes (N = 4 with diplopia and N = 3 without diplopia after GDD placement) of seven patients that had undergone placement of Baerveldt 250 (B250), Baerveldt 350 (B350), or Ahmed FP7 (FP7) GDD were prospectively enrolled at a single institution. All patients underwent a 3.0T orbital MRI with 3D volumetric T1 and T2 weighted sequence. Images were analyzed for orbital volume, axial length, orbital distances, presence of superior rectus-lateral rectus (SR-LR) band, position of GDD, and SR-LR angles. RESULTS: Patients with diplopia had smaller mean ± SD orbital axial (911.5 ± 111.8 mm3 vs 931.7 ± 79.7 mm3) and coronal volumes (1162.5 ± 145.5 mm3 vs 1180 ± 34.6 mm3) compared to non-diplopic patients. Average orbital rim distances were larger for the diplopic group. The SR-LR displacement angle for diplopic patients was larger (101.6° ± 8.1 vs 94.7° ± 17.6) while the SR-LR quadrantic angle (86.6° ± 4.2 vs 89.1° ± 4.3) was smaller. SR-LR band was present and intact in all patients. GDD malpositioning was not evident in any patient. CONCLUSION: The decreased orbital axial and coronal volumes as well as increased orbital rim distances in diplopic patients suggests the need for further studies to understand the role of orbital anatomy in occurrence of diplopia. Dynamic MRI imaging may be helpful in identifying differences in extraocular muscle function that reveal an etiology of diplopia in patients with GDD implantation.

Rates of Diplopia in Ahmed FP7, Baerveldt 250, and 350 Glaucoma Patients Compared With Medical Controls.

PRECIS: Diplopia was present in ~20% of patients with Ahmed FP7 (FP7) or Baerveldt 350 (B350), compared with 5% to 6% in those with Baerveldt 250 (B250) or controls, suggesting risk of diplopia should be included in preoperative counseling. PURPOSE: The purpose of this study was to examine the prevalence of diplopia and strabismus in patients with B250, B350, or FP7 glaucoma drainage devices (GDD). MATERIALS AND METHODS: In this cohort study, glaucoma patients 18 years and above who had received, or would be receiving, a B250, B350, or FP7 GDD, and medically treated controls were consecutively enrolled from August 8, 2017, through July 31, 2019. The Diplopia Questionnaire was administered ≥30 days postoperatively, and upon enrollment to the controls. All diplopic patients underwent orthoptic measurements, which were reviewed by a strabismus specialist. Patients with GDDs in quadrants other than superotemporal, multiple GDDs, or scleral buckles were excluded. Bonferroni correction was applied for pairwise comparisons. RESULTS: Diplopia was reported in 23/129 (17.8%) GDD patients and 5/99 (5.1%) control patients (P=0.003): 8/35 (22.9%) FP7, 2/32 (6.3%) B250, and 13/62 (21.0%) B350, with significant differences between FP7 versus controls (P=0.014) and B350 versus controls (P=0.011). Diplopia was attributable to GDD in 2 FP7 (5.9%, 95% confidence interval: 0.7-19.2), 0 B250, and 4 B350 (6.5%, 95% confidence interval: 1.7-15.2) patients, without significant differences between the GDDs. CONCLUSIONS: Patients with the larger (B350) or the higher profile plate (FP7) GDDs were more likely to experience diplopia than controls, and diplopia was attributable to the GDD in ~6% of patients with either a FP7 or a B350 GDD. Since diplopia can affect patients' quality of life, preoperative counseling for GDD surgery, particularly B350 and FP7, should include a discussion of the risk of diplopia.

Etiology of Papilledema in Patients in the Eye Clinic Setting.

Importance: The study of health conditions associated with papilledema will augment the clinical judgment of eye care professionals treating patients with optic disc edema in determining the urgency of additional evaluation and counseling patients accordingly. Objectives: To determine the incidence, demographic characteristics, and etiologies of papilledema based on a unique records-linkage research platform; and to describe the demographic and clinical differences between patients with idiopathic intracranial hypertension (IIH) and other causes of papilledema. Design, Setting, and Participants: Retrospective population-based cross-sectional study of patients treated for papilledema at outpatient eye clinics in Olmsted County, Minnesota, using the Rochester Epidemiology Project. Data were collected from January 1990 to December 2014 and analyzed from September 2018 to April 2019. Main Outcomes and Measures: Etiologies of papilledema, body mass index, incidence of headache, or localizing neurologic signs. Results: Eighty-six patients were diagnosed with papilledema during the 24-year period, providing an age- and sex-adjusted incidence of 2.5 individuals per 100 000 per year; 68 patients (79%) were women, 73 (85%) were white patients, and the median (range) age was 27.7 (6.2-64.2) years. Nineteen patients (22%) presented with a previously diagnosed attributable cause (eg, trauma or intracranial tumor). Among patients presenting with papilledema without a previously diagnosed attributable cause, 58 patients (87%) had IIH, and 9 patients (13%) were found to have a secondary cause of raised intracranial pressure, such as intracranial tumor, cerebral venous sinus thrombosis, or granulomatous meningitis. Patients with IIH had a higher median (range) body mass index (37.5 [20.4-55.7] vs 27.4 [16.6-40.1]; P = .003) and headache prevalence (54 of 58 patients [93%] vs 6 of 9 patients [67%]; P = .004) than patients with other causes of papilledema. Of 9 patients with papilledema but no IIH, 2 (22%) had localizing neurologic signs, such as gait abnormalities, hearing loss, focal weakness or numbness, visual field defects, or aphasia. Among 42 patients with demographic characteristics typically associated with IIH (female sex, with obesity, aged 15 to 45 years, and absent localizing neurologic signs or symptoms), 40 (95%) had papilledema that was associated with IIH. Conversely, among the 19 patients without these demographic characteristics, 7 (37%) had an alternative cause. Conclusions and Relevance: In this study, most patients who presented to the eye clinic with papilledema without a previously known cause were found to have IIH. These patients were more likely to present with headaches and had statistically higher body mass index. Clinicians should take these findings into account when determining the pretest probability of a patient having IIH or an alternative cause of papilledema.

Variability of Consecutive Lumbar Puncture Opening Pressures.

BACKGROUND: Lumbar puncture (LP) opening pressures (OPs) are known to fluctuate based on diurnal, environmental, and pathologic conditions. Despite their dynamic nature, single OPs are often deemed sufficient for diagnosis of elevated intracranial pressures (ICPs) in nonspecialists' hands. The purpose of this study was to determine the variability of consecutive LP OPs at a large referral center to determine the potential range of variability for a given LP OP. METHODS: In this retrospective cohort study, medical records of all patients seen at Mayo Clinic, Rochester, MN, from January 1, 2001, through June 1, 2016, were screened for ≥2 LP OPs within 30 days of each other. Patients with pathologic conditions known to influence ICP were excluded. RESULTS: There were 148 eligible patients (39.2% female) with mean age of 63.5 ± 15.5 years and mean body mass index (BMI) 28.0 ± 6.0. The LPs were a mean of 10 ± 9 days apart. Mean OP for the first and second LP was 149 ± 51 mm H2O and 148 ± 48 mm H2O (P = 0.78), respectively, with a mean difference of 1 mm H2O, providing an overall coefficient of repeatability (CR) of 86.4 between consecutive LPs. There was a significant correlation between initial OP and BMI (r = 0.39, P < 0.001). OP >200 mm H2O had a significantly higher CR of 111.4, compared to OP <200 mm H2O, with CR 74.6 (P = 0.006). CRs were also higher for patients with diagnoses of headache (P = 0.002) or anxiety (P = 0.03). CONCLUSIONS: Higher initial LP OP, headache, and anxiety were associated with greater variability on subsequent LPs. OPs that are not consistent with the patients' clinical signs and symptoms should therefore be interpreted with caution.

Population-Based Evaluation of Lumbar Puncture Opening Pressures.

Importance: Prior studies evaluating opening pressure (OP) have mostly involved lumbar puncture (LP) for diagnosis of neurologic disease or small cohorts of healthy volunteers and therefore the normal OP is not well-defined. Objective: The goal of this study was to establish the normal range of OP in a community-based population using the Mayo Clinic Study of Aging (MCSA) and to evaluate factors that contribute to OP variability. Design: LP OP were obtained from participants aged 32-95 years between 11/1/07 and 10/1/17, as part of routine data collection for the MCSA, a longitudinal, population-based study of residents of Olmsted County, Minnesota. Setting: A longitudinal, population-based study of residents of Olmsted County, Minnesota. Participants: There were 639 participants (56.8% male; 98.5% white) who underwent LP with recorded OP as part of the MCSA. Intervention: LP. Main Outcome(s) and Measure(s): LP OP was recorded along with variables that could possibly influence its variability, including age, body mass index (BMI), and obstructive sleep apnea (OSA). Results: Six hundred thirty-nine participants (56.8% men) underwent LP with recorded OP; average age was 71.0 years (SD 10.9) with a mean BMI of 28.0 (SD 4.6). Mean OP was 155.4 mmH2O (SD 41.9) with a 95% reference interval of 82-242 mmH2O (range 60-314; Q1, Q3: 124, 182). Increasing age was associated with lower OP (p < 0.001), while increasing BMI was associated with higher OP (p < 0.001). Twelve (2%) participants had OP ≥ 250 mmH2O; they were younger [58.5 (SD 8.2), p < 0.001], had higher BMI [33.6 (SD 4.6), p < 0.001], and were more likely to have OSA (75%, p < 0.001). Among the 79 participants with repeat LPs within 2.5 years, the coefficient of repeatability (CR) was 64.9. Ten (12.7%) had an OP difference ≥50 mmH2O between serial LPs. Conclusions and Relevance: This large population-based study showed that LP OP can vary significantly among individuals. Higher OPs were associated with higher BMI and younger age.

A Population-Based, Case-Control Evaluation of the Association Between Hormonal Contraceptives and Idiopathic Intracranial Hypertension.

PURPOSE: To determine if the use of oral contraceptive pills (OCP) and other hormonal contraceptives are associated with a higher incidence of idiopathic intracranial hypertension (IIH). DESIGN: Retrospective, population-based, case-control study. METHODS: Setting: Female IIH patients evaluated between January 1, 1990, and December 31, 2016 were identified using the Rochester Epidemiology Project (REP), a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. STUDY POPULATION: Fifty-three female residents of Olmsted County diagnosed with IIH between 15 and 45 years of age. The use of OCPs and other hormonal contraceptives was compared to controls matched for age, sex, and body mass index. Interventions/Exposures: Hormonal contraceptives. MAIN OUTCOME MEASURE: Odds of developing IIH. RESULTS: Of the 53 women diagnosed with IIH between 15 and 45 years of age, 11 (20.8%) had used hormonal contraceptives within ≤30 days of the date of IIH diagnosis, in contrast to 30 (31.3%) among the control patients. The odds ratio of hormonal contraceptive use and IIH was 0.55 (95% conficence interval [CI]: 0.24-1.23, P = .146). The odds ratio of OCP use was 0.52 (95% CI: 0.20-1.34, P = .174). CONCLUSIONS: OCP and other hormonal contraceptives were not significantly associated with a higher incidence of IIH, arguing against the need for women with IIH to discontinue their use.

Re-evaluating the Incidence of Idiopathic Intracranial Hypertension in an Era of Increasing Obesity.

PURPOSE: To re-evaluate the population-based incidence of idiopathic intracranial hypertension (IIH) and to determine if it mirrors the rise in obesity. DESIGN: Retrospective, population-based cohort. PARTICIPANTS: All residents of Olmsted County, Minnesota, diagnosed with IIH between January 1, 1990, and December 31, 2014. METHODS: All cases of IIH were identified using the Rochester Epidemiology Project, which is a record-linkage system of medical records for all patient-physician encounters among Olmsted County, Minnesota, residents. All medical records were reviewed to confirm a diagnosis of IIH. The incidence rates of IIH were compared against the incidence of obesity in Minnesota over the same period. MAIN OUTCOME MEASURES: Incidence of IIH, lumbar puncture opening pressures, and body mass index. RESULTS: There were 63 new cases of IIH, yielding an overall age- and gender-adjusted annual incidence of 1.8 per 100 000 (95% confidence interval, 1.3-2.2) between 1990 and 2014. It increased from 1.0 per 100 000 (1990-2001) to 2.4 per 100 000 (2002-2014; P = 0.007). The incidence of IIH was 3.3 per 100 000 in women and 0.3 per 100 000 in men (P ≤ 0.001). In obese women 15 to 44 years of age, the incidence was 22.0 per 100 000 compared with 6.8 per 100 000 among all women in the same age group. A strong correlation was observed between IIH incidence rates and obesity rates in Minnesota (R2 = 0.70, P = 0.008). CONCLUSIONS: The incidence of IIH has increased since 1990, which is highly correlated with the rise in obesity during the same period.

Surgical correction of childhood intermittent exotropia and the risk of developing mental illness.

PURPOSE: To assess whether successful surgical intervention for intermittent exotropia, or the timing of intervention, has any effect on the development of mental illness. DESIGN: Retrospective, observational case series. METHODS: All patients (<19 years of age) diagnosed with intermittent exotropia in Olmsted County, Minnesota, from January 1, 1975, through December 31, 1994, were reviewed retrospectively. Potential cases were identified using the resources of the Rochester Epidemiology Project, a medical records database designed to capture data on any patient-physician encounter in Olmsted County, Minnesota. The main outcome measures were the occurrence and severity of mental illness among those who underwent strabismus surgery compared with those who did not. RESULTS: Ninety-six (52%) of the 184 children identified were diagnosed with a mental illness at a mean age of 23.3 years (range, 6 to 41 years). Thirty-five (36%) of the 96 children in whom mental illness developed underwent strabismus surgery. Success at surgery (<10 prism diopters) was not associated with a decreased occurrence of mental illness (P = .30). Of the 88 patients in whom mental illness did not develop, strabismus surgery was not more commonly performed (P = .54), nor was it performed at a younger age (P = 1.0), when compared with the 96 patients in whom mental illness developed later. CONCLUSIONS: Strabismus surgery for children with intermittent exotropia, regardless of success or age at surgery, did not alter the development of mental illness by early adulthood.