Sandra S. Stinnett

Intracranial Pressure in Primary Open Angle Glaucoma, Normal Tension Glaucoma, and Ocular Hypertension: A Case–Control Study

PURPOSE To compare intracranial pressure (ICP) in subjects with primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG; subset of POAG), and ocular hypertension (OHT) with that in subjects with no glaucoma. METHODS The study was a retrospective review of medical records of 62,468 subjects who had lumbar puncture between 1985 and 2007 at the Mayo Clinic. Of these, 57 POAG subjects, 11 NTG subjects (subset of POAG), 27 OHT subjects, and 105 control subjects met the criteria and were analyzed. A masked comparison of the relationship between ICP and other ocular and nonocular variables was performed by using univariate and multivariate analyses. RESULTS ICP was significantly lower in POAG compared with age-matched control subjects with no glaucoma (9.1 +/- 0.77 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.0001). Subjects with NTG also had reduced ICP compared with the control subjects (8.7 +/- 1.16 mm Hg vs. 11.8 +/- 0.71 mm Hg; P < 0.01). ICP was higher in OHT than in age-matched control subjects (12.6 +/- 0.85 mm Hg vs. 10.6 +/- 0.81 mm Hg; P < 0.05). CONCLUSIONS ICP is lower in POAG and NTG and elevated in OHT. ICP may play an important role in the development of POAG and NTG and in preventing the progression of OHT to POAG. Further prospective and experimental studies are warranted to determine whether ICP has a fundamental role in the pathogenesis of glaucoma.

A benefit of spinal manipulation as adjunctive therapy for acute low-back pain: a stratified controlled trial.

Fifty-four subjects volunteered to participate in a controlled study contrasting spinal manipulation with spinal mobilization without the rotational forces and leverage required to move facet joints. All suffered from regional low-back pain for less than 1 month, were ages 18–40, had never previously undergone any form of spinal manipulation, and denied a prior episode of backache within the previous 6 months. Randomization was stratified at outset into those who suffered for less than 2 weeks and those whose discomfort had persisted for 2–4 weeks. Outcome was monitored by a questionnaire assessing functional impairment. A treatment effect of manipulation was demonstrated only in the strata with more prolonged illness at entry. In the first week following manipulation, these patients improved to a greater degree (P=.009, t test) and more rapidly (P <.025, Wilcoxon rank-sum test).

Meta-analysis of plasma homocysteine, serum folate, serum vitamin B12, and thermolabile MTHFR genotype as risk factors for retinal vascular occlusive disease

PURPOSE To assess the role of plasma total homocysteine (tHcy) levels, serum folate and vitamin B(12)levels, and homozygosity for the thermolabile methylenetetrahydrofolate reductase genotype (TT) as risk factors for retinal vascular occlusive disease. DESIGN Meta-analysis of literature. METHODS A MEDLINE search was performed to identify all published case-control studies of plasma tHcy levels, serum folate and vitamin B(12) levels, and TT genotype in persons with retinal vascular occlusive disease. Main outcome measures included calculation of plasma tHcy, serum folate, and serum vitamin B(12) standard differences and odds ratios (OR) of TT genotype between cases and controls. RESULTS In total, 614 patients with all types of retinal vein occlusion had higher plasma tHcy levels than 762 control subjects (standard difference, 0.867; 95% confidence interval [CI] = 0.735, 0.999; P <.001). Plasma tHcy levels were also higher in 154 patients with retinal artery occlusion compared with 358 control subjects (standard difference 1.174; 95% CI = 0.947, 1.402; P <.001). Serum folates, but not vitamin B(12) levels, were lower in 287 patients with retinal vascular occlusion than in the same number of control subjects (standard difference, 0.508; 95% CI = 0.340, 0.675; P <.001; and -0.060; 95% CI = -0.024, 0.104; P =.474, respectively). Similar proportions of 690 patients with retinal vein occlusion and 2754 control subjects demonstrated the TT genotype (OR = 1.332; 95% CI = 0.995, 1.783; P =.054) as did 152 patients with retinal artery occlusions and 435 control subjects (OR = 1.716; 95% CI = 0.977, 3.014; P =.060). CONCLUSIONS Retinal vascular occlusion is associated with elevated plasma tHcy levels and low serum folate levels, but not serum vitamin B(12) levels and TT genotype. Until a prospective multicenter trial is undertaken, plasma tHcy levels and serum folate levels should be determined in patients with retinal vascular occlusions, and dietary supplementation with low doses of folate and vitamin B(12) should be considered for affected persons.

Clinical Practice Guideline: Acute Otitis Externa

OBJECTIVE: This guideline provides evidence-based recommendations to manage diffuse acute otitis externa (AOE), defined as generalized inflammation of the external ear canal, which may also involve the pinna or tympanic membrane. The primary purpose is to promote appropriate use of oral and topical antimicrobials and to highlight the need for adequate pain relief. STUDY DESIGN: In creating this guideline, the American Academy of Otolaryngology-Head and Neck Surgery Foundation (AAO-HNSF) selected a development group representing the fields of otolaryngology-head and neck surgery, pediatrics, family medicine, infectious disease, internal medicine, emergency medicine, and medical informatics. The guideline was created with the use of an explicit, a priori, evidence-based protocol. RESULTS: The group made a strong recommendation that management of AOE should include an assessment of pain, and the clinician should recommend analgesic treatment based on the severity of pain. The group made recommendations that clinicians should: 1) distinguish diffuse AOE from other causes of otalgia, otorrhea, and inflammation of the ear canal; 2) assess the patient with diffuse AOE for factors that modify management (nonintact tympanic membrane, tympanostomy tube, diabetes, immunocompromised state, prior radiotherapy); and 3) use topical preparations for initial therapy of diffuse, uncomplicated AOE; systemic antimicrobial therapy should not be used unless there is extension outside of the ear canal or the presence of specific host factors that would indicate a need for systemic therapy. The group made additional recommendations that: 4) the choice of topical antimicrobial therapy of diffuse AOE should be based on efficacy, low incidence of adverse events, likelihood of adherence to therapy, and cost; 5) clinicians should inform patients how to administer topical drops, and when the ear canal is obstructed, delivery of topical preparations should be enhanced by aural toilet, placing a wick, or both; 6) when the patient has a tympanostomy tube or known perforation of the tympanic membrane, the clinician should prescribe a nonototoxic topical preparation; and 7) if the patient fails to respond to the initial therapeutic option within 48 to 72 hours, the clinician should reassess the patient to confirm the diagnosis of diffuse AOE and to exclude other causes of illness. And finally, the panel compiled a list of research needs based on limitations of the evidence reviewed. CONCLUSION: This clinical practice guideline is not intended as a sole source of guidance in evaluating patients with AOE. Rather, it is designed to assist clinicians by providing an evidence-based framework for decision-making strategies. It is not intended to replace clinical judgment or establish a protocol for all individuals with this condition and may not provide the only appropriate approach to the diagnosis and management of this problem. SIGNIFICANCE: This is the first, explicit, evidence-based clinical practice guideline on acute otitis externa, and the first clinical practice guideline produced independently by the AAO-HNSF.

Dynamics of Human Foveal Development after Premature Birth

PURPOSE To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT). DESIGN Prospective, observational case series. PARTICIPANTS Thirty-one prematurely born neonates, 9 children, and 9 adults. METHODS Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 μm from the foveal center), and 3-dimensional thickness maps were analyzed. MAIN OUTCOME MEASURES In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting. RESULTS In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation. CONCLUSIONS This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable SD-OCT. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity and a method for mapping foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Cellular senescence in the glaucomatous outflow pathway.

The mechanisms responsible for the progressive malfunction of the trabecular meshwork (TM)-Schlemms canal (SC) conventional outflow pathway tissue in primary open angle glaucoma (POAG) are still not fully understood. To determine whether POAG is characterized by an accumulation of senescent cells, similar to what has been described in other diseases, we have compared the levels of the senescence marker senescence-associated-beta-galactosidase (SA-beta-gal) in the outflow pathway cells of POAG and age-matched control donors. POAG donors demonstrated a statistically significant fourfold increase in the percentage of SA-beta-gal positive cells. These results suggest a potential role for cellular senescence in the pathophysiology of the outflow pathway.

Spectral Domain Optical Coherence Tomography Imaging of Geographic Atrophy Margins

OBJECTIVE To test in vivo whether spectral domain optical coherence tomography (SD-OCT) provides adequate resolution for reproducible measurement of photoreceptor (PR) layer at the margins of geographic atrophy (GA), and if it delineates the relationship between PR layer and retinal pigment epithelium at the margins of GA. DESIGN Prospective consecutive case series. PARTICIPANTS Patients with GA secondary to nonneovascular age-related macular degeneration (AMD) identified during routine follow-up at Duke Eye Center between January 3, 2006, and June 3, 2007, and who consented to participate in this study. METHODS We used SD-OCT to image eyes. Multiple B-scans from each eye were saved and independently graded by 2 graders and the following locations were marked: (1) site where PR thickness began to decline below its baseline, (2) site where PR layer disappeared, and (3) site of the GA margin. These data were processed to calculate the locations of PR losses relative to GA margins and were categorized as (A) bridging across GA margins, (B) entirely within GA margins, or (C) entirely outside GA margins. MAIN OUTCOME MEASURES Location of PR loss (bridging across GA margins, entirely within GA margins, or entirely outside GA margins) was calculated. Distances from the GA margin were measured for beginning and ending of PR loss. Interobserver agreement was determined for categories of PR loss as well as locations of PR loss relative to the GA margin. RESULTS We analyzed 500 unique scans. The PR loss occurred most frequently bridging across the GA margin (65% scans), second most frequently entirely inside the GA margin (29% scans), and least frequently entirely outside the GA margin (6% scans). Loss of PR started an average of 61 microm (standard deviation [SD] +/- 235) outside the GA margin, ended an average of 311+/-273 microm inside the GA margin, and spanned an average of 372+/-179 microm. CONCLUSIONS Relative to GA margins in non-neovascular AMD with GA, SD-OCT provides adequate resolution for quantifying PR loss. It may also serve as a means of tracking disease progression in future interventional trials. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Trends in the indications for penetrating keratoplasty, 1980-2001.

Purpose: To study the leading indications and changing trends for penetrating keratoplasty (PK) over the past 3 decades. Methods: This is a retrospective review of 696 cases of PK. The indications for PKs performed at the Duke University Eye Center during the years 1980-1981, 1990- 1991, and 2000-2001 were tabulated to determine trends over the past 3 decades. The main outcome measures were indications for PK. Results: During this study, 696 PKs were performed. The leading indications for PK and their respective frequencies during 1980-1981, 1990-1991, and 2000-2001 were failed grafts (10.8%, 19.0%, 27.0%, respectively), pseudophakic bullous keratopathy (PBK)/aphakic bullous keratopathy (ABK) (19.4%, 20.6%, 16.7%, respectively), Fuchs dystrophy (15.6%, 13.0%, 23.8%, respectively), keratoconus (13.4%, 8.2%, 11.8%, respectively), and corneal scar (7.0%, 8.9%, 10.7%, respectively). The number of PKs for failed grafts and Fuchs dystrophy increased over time. Conclusions: In this study, failed graft has gradually become the leading indication for PK, whereas most other studies have reported PBK as the leading indication. Unlike many other studies, Fuchs dystrophy was a common indication for PK.

Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. Effect of patient characteristics on lovastatin-induced changes in plasma concentrations of lipids and lipoproteins.

Background Lovastatin produces consistent dose-related reductions in plasma levels of low density lipoprotein (LDL) cholesterol along with variable decreases in triglycerides and increases in high density lipoprotein (HDL) cholesterol. Patient characteristics from the Expanded Clinical Evaluation of Lovastatin (EXCEL) study were examined to determine their association with the magnitude of lovastatin-induced changes in these lipids and lipoproteins. Methods and Results After a baseline period consisting of dietary therapy, 8,245 patients with moderate hypercholesterolemia were randomized to five groups that received 48 weeks of treatment with either placebo or daily doses of lovastatin ranging from 20 to 80 mg. By use of linear statistical models, 20 different patient characteristics were examined for modification of the dose-dependent responses observed. For LDL cholesterol, the following were associated with enhanced lowering (p < 0.05; percent changes are placebo-corrected, adjusted mean changes from baseline for the 80-mg/day lovastatin group): full drug compliance (−41.9%) versus 80% compliance (−20.3%); an age of 65 (−43.4%) versus 45 years (−38.1%) for women; white race (−40.9%) versus black race (−38.0%); and 4.5-kg weight gain (−42.6%) versus 4.5-kg weight loss (−37.9%). Similar relations for enhanced triglyceride lowering were found with older age and weight gain. Patients with initially low HDL cholesterol (<0.91 mmol/l) and high triglycerides (>2.26 mmol/l) had enhanced responses for these parameters: placebo-corrected percent changes at 80 mg/day were −27.4% for triglycerides and +12.3% for HDL cholesterol. Conclusions Overall, patient characteristics had very little impact of clinical importance on the dose-dependent LDL cholesterol lowering found with lovastatin. In patients with initially high levels of triglycerides and low levels of HDL cholesterol, the elevation of HDL cholesterol produced by lovastatin appears to be enhanced.

High failure rate associated with 180 degrees selective laser trabeculoplasty.

Purpose:To determine the efficacy of selective laser trabeculoplasty (SLT) in a tertiary care referral center. Patients and Methods:In this retrospective study of selective laser trabeculoplasty performed by five physicians, 94 eyes from 94 patients were included. A majority (83/92, 90%) underwent 180° selective laser trabeculoplasty. Selective laser trabeculoplasty failure was defined in two ways: (1) IOP decrease <3 mm Hg (definition one), or (2) IOP decrease <20% (definition two), on two successive visits ≥4 weeks after SLT. Results:Overall failure rates were 68% (64/94) and 75% (70/94) (by definitions one and two, respectively). By survival/life-table analysis, mean time to failure was 6 months and 5.5 months, by definitions one and two, respectively. By the end of the study (14.5 months), the failure rates were 86% and 92% by definitions one and two, respectively. By each definition, in both univariable and multivariable analysis, only lower baseline IOP was a significant predictor of failure. Conclusions:Selective laser trabeculoplasty had an overall low success rate in our tertiary clinic population, with overall failure rates of 68% to 74% in those who underwent 180° selective laser trabeculoplasty.