New York Eye and Ear Infirmary

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.

Primary open-angle glaucoma (POAG) affects 33 million individuals worldwide and is a leading cause of blindness. In a study of 54 families with autosomal dominantly inherited adult-onset POAG, we identified the causative gene on chromosome 10p14 and designated it OPTN (for "optineurin"). Sequence alterations in OPTN were found in 16.7% of families with hereditary POAG, including individuals with normal intraocular pressure. The OPTN gene codes for a conserved 66-kilodalton protein of unknown function that has been implicated in the tumor necrosis factor-alpha signaling pathway and that interacts with diverse proteins including Huntingtin, Ras-associated protein RAB8, and transcription factor IIIA. Optineurin is expressed in trabecular meshwork, nonpigmented ciliary epithelium, retina, and brain, and we speculate that it plays a neuroprotective role.

Interleukin-17A (IL-17A) is elaborated by the T helper 17 (T(H)17) subset of T(H) cells and exhibits potent proinflammatory properties in animal models of autoimmunity, including collagen-induced arthritis, experimental autoimmune encephalomyelitis, and experimental autoimmune uveitis. To determine whether IL-17A mediates human inflammatory diseases, we investigated the efficacy and safety of AIN457, a human antibody to IL-17A, in patients with psoriasis, rheumatoid arthritis, and chronic noninfectious uveitis. Patients with chronic plaque-type psoriasis (n = 36), rheumatoid arthritis (n = 52), or chronic noninfectious uveitis (n = 16) were enrolled in clinical trials to evaluate the effects of neutralizing IL-17A by AIN457 at doses of 3 to 10 mg/kg, given intravenously. We evaluated efficacy by measuring the psoriasis area and severity index (PASI), the American College of Rheumatology 20% response (ACR20) for rheumatoid arthritis, or the number of responders for uveitis, as defined by either vision improvement or reduction in ocular inflammation or corticosteroid dose. AIN457 treatment induced clinically relevant responses of variable magnitude in patients suffering from each of these diverse immune-mediated diseases. Variable response rates may be due to heterogeneity in small patient populations, differential pathogenic roles of IL-17A in these diseases, and the different involvement or activation of IL-17A-producing cells. The rates of adverse events, including infections, were similar in the AIN457 and placebo groups. These results support a role for IL-17A in the pathophysiology of diverse inflammatory diseases including psoriasis, rheumatoid arthritis, and noninfectious uveitis.

Purpose: The aim of this study was to recommend protocols for instrumental assessment of voice production in the areas of laryngeal endoscopic imaging, acoustic analyses, and aerodynamic procedures, which will (a) improve the evidence for voice assessment measures, (b) enable valid comparisons of assessment results within and across clients and facilities, and (c) facilitate the evaluation of treatment efficacy. Method: Existing evidence was combined with expert consensus in areas with a lack of evidence. In addition, a survey of clinicians and a peer review of an initial version of the protocol via VoiceServe and the American Speech-Language-Hearing Association's Special Interest Group 3 (Voice and Voice Disorders) Community were used to create the recommendations for the final protocols. Results: The protocols include recommendations regarding technical specifications for data acquisition, voice and speech tasks, analysis methods, and reporting of results for instrumental evaluation of voice production in the areas of laryngeal endoscopic imaging, acoustics, and aerodynamics. Conclusion: The recommended protocols for instrumental assessment of voice using laryngeal endoscopic imaging, acoustic, and aerodynamic methods will enable clinicians and researchers to collect a uniform set of valid and reliable measures that can be compared across assessments, clients, and facilities.

To report nine cases of pachychoroid pigment epitheliopathy.An observational case series of nine patients who underwent comprehensive ophthalmic examination, fundus photography, fundus autofluorescence, spectral-domain optical coherence tomography, and enhanced depth imaging optical coherence tomography.Eighteen eyes of 9 patients, aged 27 years to 89 years, were diagnosed with pachychoroid pigment epitheliopathy based on the characteristic funduscopic appearance of reduced fundus tessellation with overlying retinal pigment epithelial changes in one or both eyes, fundus autofluorescence abnormalities, and increased subfoveal choroidal thickness confirmed by enhanced depth imaging optical coherence tomography (mean, 460.2 μm). The five older patients had been previously diagnosed with age-related macular degeneration, while the four younger subjects were referred for possible inflammatory chorioretinitis, pattern dystrophy, or nonspecific drusen. No subjects had a history of or subsequently developed subretinal fluid.Pachychoroid pigment epitheliopathy falls within a spectrum of diseases associated with choroidal thickening that includes central serous chorioretinopathy and polypoidal choroidal vasculopathy, and it should be suspected in eyes with a characteristic fundus appearance related to choroidal thickening and associated retinal pigment epithelial abnormalities but no history of subretinal fluid. Enhanced depth imaging optical coherence tomography confirming an abnormally thick choroid and characteristic retinal pigment epithelial changes on fundus autofluorescence support the diagnosis. Because these patients are frequently misdiagnosed, the recognition of pachychoroid pigment epitheliopathy may avoid unnecessary diagnostic testing and interventions.

A glaucoma locus, GLC1A, was identified previously on chromosome 1q. A gene within this locus (encoding the protein myocilin) subsequently was shown to harbor mutations in 2-4% of primary open angle glaucoma patients. A total of 1703 patients was screened from five different populations representing three racial groups. There were 1284 patients from primarily Caucasian populations in Iowa (727), Australia (390) and Canada (167). A group of 312 African American patients was from New York City and 107 Asian patients from Japan. Overall, 61 different myocilin sequence variations were identified. Of the 61 variations, 21 were judged to be probable disease-causing mutations. The number of probands found to harbor such mutations in each population was: Iowa 31/727 (4.3%), African Americans from New York City 8/312 (2.6%), Japan 3/107 (2.8%), Canada 5/167 (3.0%), Australia 11/390 (2.8%) and overall 58/1703 (3. 4%). Overall, 16 (76%) of 21 mutations were found in only one population. The most common mutation observed, Gln368Stop, was found in 27/1703 (1.6%) glaucoma probands and was found at least once in all groups except the Japanese. Studies of genetic markers flanking the myocilin gene suggest that most cases of the Gln368Stop mutations are descended from a common founder. Although the specific mutations found in each of the five populations were different, the overall frequency of myocilin mutations was similar ( approximately 2-4%) in all populations, suggesting that the increased rate of glaucoma in African Americans is not due to a higher prevalence of myocilin mutations.

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

PURPOSE: To describe a new method of retinal vascular perfusion density mapping using optical coherence tomography angiography and to compare current staging of diabetic retinopathy based on clinical features with a new grading scale based on perifoveal perfusion densities. METHODS: A retrospective review was performed on subjects with diabetic retinopathy and age-matched controls imaged with a spectral domain optical coherence tomography system (Optovue XR Avanti, Fremont, CA). Split-spectrum amplitude-decorrelation angiography (SSADA) generated optical coherence tomography angiograms of the superficial retinal capillaries, deep retinal capillaries, and choriocapillaris. Skeletonized optical coherence tomography angiograms were used to create color-coded perfusion maps and capillary perfusion density values for each image. Capillary perfusion density values were compared with clinical staging, and groups were compared using analysis of variance and Kruskal-Wallis analyses. RESULTS: Twenty-one control and 56 diabetic retinopathy eyes were imaged. Diabetic eyes were grouped according to clinical stage. Capillary perfusion density values from each microvascular layer were compared across all groups. Capillary perfusion density values were significantly lower in nearly all layers of all study groups compared with controls. Trend analysis showed a significant decrease in capillary perfusion density values as retinopathy progresses for most layers. CONCLUSION: Quantitative retinal vascular perfusion density mapping agreed closely with grading based on clinical features and may offer an objective method for monitoring disease progression in diabetic retinopathy.

IMPORTANCE: To our knowledge, there are no large prospective cohorts of untreated patients with idiopathic intracranial hypertension (IIH) to characterize the disease. OBJECTIVE: To report the baseline clinical and laboratory features of patients enrolled in the Idiopathic Intracranial Hypertension Treatment Trial. DESIGN, SETTING, AND PARTICIPANTS: We collected data at baseline from questionnaires, examinations, automated perimetry, and fundus photography grading. Patients (n = 165) were enrolled from March 17, 2010, to November 27, 2012, at 38 academic and private practice sites in North America. All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation between -2 dB and -7 dB. All but 4 participants were women. MAIN OUTCOMES AND MEASURES: Baseline and laboratory characteristics. RESULTS: The mean (SD) age of our patients was 29.0 (7.4) years and 4 (2.4%) were men. The average (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 39.9 (8.3). Headache was the most common symptom (84%). Transient visual obscurations occurred in 68% of patients, back pain in 53%, and pulse synchronous tinnitus in 52%. Only 32% reported visual loss. The average (SD) perimetric mean deviation in the worst eye was -3.5 (1.1) dB, (range, -2.0 to -6.4 dB) and in the best eye was -2.3 (1.1) dB (range, -5.2 to 0.8 dB). A partial arcuate visual field defect with an enlarged blind spot was the most common perimetric finding. Visual acuity was 85 letters or better (20/20) in 71% of the worst eyes and 77% of the best eyes. Quality of life measures, including the National Eye Institute Visual Function Questionnaire-25 and the Short Form-36 physical and mental health summary scales, were lower compared with population norms. CONCLUSIONS AND RELEVANCE: The Idiopathic Intracranial Hypertension Treatment Trial represents the largest prospectively analyzed cohort of untreated patients with IIH. Our data show that IIH is almost exclusively a disease of obese young women. Patients with IIH with mild visual loss have typical symptoms, may have mild acuity loss, and have visual field defects, with predominantly arcuate loss and enlarged blind spots that require formal perimetry for detection. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01003639.

<ns3:p> The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at <ns3:ext-link xmlns:ns4="http://www.w3.org/1999/xlink" ext-link-type="uri" ns4:href="https://github.com/dib-lab/khmer/">https://github.com/dib-lab/khmer/</ns3:ext-link> . </ns3:p>

BACKGROUND: Hypertrophic pachymeningitis is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been associated with rheumatoid arthritis, syphilis, Wegener's granulomatosis, tuberculosis, and cancer. Few series of the idiopathic variety have been described, particularly with respect to MRI correlation to clinical outcome and treatment. OBJECTIVE: To investigate the clinical and laboratory evaluation, course, and treatment of patients with idiopathic hypertrophic pachymeningitis (IHP), to correlate the MRI findings with the clinical course, and to review the literature on IHP. METHODS: Retrospective case series of 12 patients (9 men, 3 women), with a mean age of 55 years (range 39 to 88 years), who had IHP by imaging studies, meningeal or orbital biopsy, or both. The clinical features, laboratory evaluation, contrast-enhanced MRI, treatment, and clinical outcome were documented for each case. The mean duration of follow-up was 3.5 years (range 3 months to 16 years). RESULTS: The main clinical features at presentation were headache (11 cases), loss of vision (7 cases), diplopia (4 cases), papilledema (2 cases), other cranial nerve involvement (3 cases), ataxia (2 cases), and seizures (1 case). On the initial MRI, the location of abnormal enhancement of the dura mater correlated with the clinical findings and the sphenoid wing area was affected in all patients. The sedimentation rate was elevated in five cases. The CSF had increased protein in six cases and lymphocytosis in four cases. Biopsy of the dura mater in five cases and the orbital soft tissue in one case showed infiltrates of small mature lymphocytes, plasma cells, and epithelioid histiocytes, but no neoplasia, vasculitis, or infectious agents. Cultures of the CSF and biopsy material remained sterile. Corticosteroid therapy improved the vision in 7 of 8 cases and controlled headache in 10 of 11 cases. Five cases had partial improvement of other neurologic symptoms and signs. Recurrence developed with steroid tapering in six cases. One case had progressive deterioration and died. In four cases methotrexate or azathioprine was added with reduction of the steroid dose. Follow-up MRI performed in 11 patients correlated 80% with the clinical state (p = 0.01). CONCLUSION: IHP can be suspected on MRI and defined pathologically on biopsy. Untreated, the clinical course is usually marked by severe headache and progressive neurologic deterioration and vision loss. Although initially steroid-responsive, clinical manifestations frequently recur with corticosteroid taper, requiring the addition of immunosuppressive agents in some cases.

Topical ophthalmic, oral, and intravenous corticosteroids have long been associated with ocular side effects. Recent data suggest that inhaled corticosteroids are also associated with the development of cataract and increased intraocular pressure. Thus far, nasally administered steroids have not been associated with the same effects. Local injection of steroids, even at sites far from the eye, have been associated with the development of cataract, glaucoma, and even retinal and choroidal emboli. Any physician prescribing corticosteroids should be aware of these potential ocular side effects and should advise patients accordingly.

Clinical electrophysiological testing of the visual system incorporates a range of noninvasive tests and provides an objective indication of function relating to different locations and cell types within the visual system. This document developed by the International Society for Clinical Electrophysiology of Vision provides an introduction to standard visual electrodiagnostic procedures in widespread use including the full-field electroretinogram (ERG), the pattern electroretinogram (pattern ERG or PERG), the multifocal electroretinogram (multifocal ERG or mfERG), the electrooculogram (EOG) and the cortical-derived visual evoked potential (VEP). The guideline outlines the basic principles of testing. Common clinical presentations and symptoms are described with illustrative examples and suggested investigation strategies.

OBJECTIVE: To examine the temporal changes in head and neck cancer in young adults in the United States. METHODS: Using the cancer surveillance database from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program, we calculated age-adjusted incidence rates for head and neck cancers. Using the joinpoint regression model, we described tongue cancer incidence trends and established the statistical significance of temporal changes. We also compared changes in 5-year survival rates for tongue cancer. RESULTS: From 1973 to 1997, there were 63 409 patients with head and neck cancer in the 9 SEER registries. Of these, 3339 patients were younger than 40 years. The incidence of head and neck cancer remained stable in groups older than 40 years comparing the 1973-1984 and 1985-1997 data. In contrast, tongue cancer in adults younger than 40 years increased approximately 60% during the same period. We detected a significant increase until 1985, the estimated annual percentage change being 6.7% (95% confidence interval, 2.7%-10.8%; P<.001). After 1985, incidence rates stopped rising but remained steadily high. The change in tongue cancer incidence rates for young adults was related to birth cohorts between 1938 and 1948. The absolute increase in 5-year survival for tongue cancer ranged from 11.7% (<40 years old) to 6.6% (40-64 years old) between 1973-1984 and 1985-1997, with the most significant improvement occurring in young Americans with regional or distant disease (27% and 21%, respectively). CONCLUSIONS: A sharp increasing trend in tongue cancer in young Americans may be attributed to persons born after 1938. The reason for the increase is uncertain. Improved survival rates in young patients suggest the emergence of a distinct disease process that is apparent in white but not black populations.

BACKGROUND: Without treatment, congenital toxoplasmosis has recurrent, recrudescent, adverse outcomes. Long-term follow-up of infants with congenital toxoplasmosis treated throughout their first year of life with pyrimethamine and sulfadiazine has not been reported. METHODS: Between 1981 and 2004, one hundred twenty infants (current mean age +/- standard deviation, 10.5 +/- 4.8 years) with congenital toxoplasmosis were treated with 1 of 2 doses of pyrimethamine plus sulfadiazine; therapy was initiated shortly after birth and continued for 12 months. Children who received treatment were evaluated at birth and at predetermined intervals; the focus of the evaluations was on prespecified end points: motor abnormalities, cognitive outcome, vision impairment, formation of new eye lesions, and hearing loss. RESULTS: Treatment of infants without substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1 year resulted in normal cognitive, neurologic, and auditory outcomes for all patients. Treatment of infants who had moderate or severe neurologic disease (as defined in this article in the Treatments subsection of Methods) at birth resulted in normal neurologic and/or cognitive outcomes for >72% of the patients, and none had sensorineural hearing loss. Ninety-one percent of children without substantial neurologic disease and 64% of those with moderate or severe neurologic disease at birth did not develop new eye lesions. Almost all of these outcomes are markedly better than outcomes reported for children who were untreated or treated for 1 month in earlier decades (P<.01 to P<.001). Sex and severity of disease were comparable in our 2 treatment groups, and no significant differences in efficacy or toxicity were noted between the 2 treatment groups (P > .05). CONCLUSIONS: Although not all children did well with treatment, the favorable outcomes we noted indicate the importance of diagnosis and treatment of infants with congenital toxoplasmosis.

OBJECTIVE: To determine intraocular pressure (IOP)-dependent and IOP-independent variables associated with visual field (VF) progression in treated glaucoma. DESIGN: Retrospective cohort of the Glaucoma Progression Study. METHODS: Consecutive, treated glaucoma patients with repeatable VF loss who had 8 or more VF examinations of either eye, using the Swedish Interactive Threshold Algorithm (24-2 SITA-Standard, Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc, Dublin, California), during the period between January 1999 and September 2009 were included. Visual field progression was evaluated using automated pointwise linear regression. Evaluated data included age, sex, race, central corneal thickness, baseline VF mean deviation, mean follow-up IOP, peak IOP, IOP fluctuation, a detected disc hemorrhage, and presence of beta-zone parapapillary atrophy. RESULTS: We selected 587 eyes of 587 patients (mean [SD] age, 64.9 [13.0] years). The mean (SD) number of VFs was 11.1 (3.0), spanning a mean (SD) of 6.4 (1.7) years. In the univariable model, older age (odds ratio [OR], 1.19 per decade; P = .01), baseline diagnosis of exfoliation syndrome (OR, 1.79; P = .01), decreased central corneal thickness (OR, 1.38 per 40 μm thinner; P < .01), a detected disc hemorrhage (OR, 2.31; P < .01), presence of beta-zone parapapillary atrophy (OR, 2.17; P < .01), and all IOP parameters (mean follow-up, peak, and fluctuation; P < .01) were associated with increased risk of VF progression. In the multivariable model, peak IOP (OR, 1.13; P < .01), thinner central corneal thickness (OR, 1.45 per 40 μm thinner; P < .01), a detected disc hemorrhage (OR, 2.59; P < .01), and presence of beta-zone parapapillary atrophy (OR, 2.38; P < .01) were associated with VF progression. CONCLUSIONS: IOP-dependent and IOP-independent risk factors affect disease progression in treated glaucoma. Peak IOP is a better predictor of progression than is IOP mean or fluctuation.

Radiotherapy offers patients with malignant melanoma of the choroid an eye and a vision-sparing alternative to enucleation. The most commonly used forms of radiotherapy are ophthalmic plaque brachytherapy and charged-particle (external beam) radiotherapy. Unfortunately, after all forms of radiotherapy for choroidal melanoma many patients experience sight-limiting side effects, and an average of 16.3% of patients treated with radiotherapy subsequently require enucleation because of tumor regrowth or uncontrollable neovascular glaucoma. The severity, location, and incidence of radiation-induced complications are related to the type of radiation used, its method of delivery, amount of radiation delivered to normal ocular structures, the size and location of the tumor, as well as its response to irradiation. Current research is directed toward developing methods to reduce the amount of radiation delivered to normal structures, e.g., adding heat to radiotherapy. The true viability and metastatic potential of irradiated uveal melanoma cells has not been established, although clinical studies have reported local control of choroidal melanoma in 81-100% (mean = 92.8%) of cases. The purpose of this review is to present the world's experience with radiotherapy for choroidal melanoma, information that will contribute to patient education and informed consent.

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers.

OBJECTIVES/HYPOTHESIS: To define the prevalence of tracheotomy tube complications and evaluate risk factors (RFs) associated with their occurrence. STUDY DESIGN: Multi-institution historical cohort. METHODS: Data regarding tracheotomy tube complications from consecutive surgeries performed across eight participating institutions between January 1, 2008 and December 31, 2009 were retrospectively collected. Patient demographics, comorbidities, physician specialty, and surgical technique were recorded and statistically analyzed to identify the incidence of surgical complications following tracheotomy and associated RFs. RESULTS: The charts of 1,175 tracheotomy procedures were reviewed from eight academic institutions. Otolaryngologists performed 66.2% of the tracheotomies. Intraoperative, early (<1 week), and late complication rates were 1.4%, 5.6%, and 7.1%, respectively. Postoperative bleeding was identified as the most common early complication (2.6%), whereas airway stenosis was the most common late complication (1.7%). The use of outer flange security sutures to anchor the tracheostomy tube was negatively associated with the incidence of early complication (P<.0001). The use of large endotracheal tubes (size>7.5) and obesity were associated with the development of airway stenosis (P<.05).Twenty-two percent of patients undergoing tracheotomy died during hospitalization. CONCLUSIONS: Perioperative tracheotomy complications are rare; however, the rate of death for all causes is high (22%) in this population. Obesity and the use of endotracheal tubes over 7.5 in size are major risk factors for the development of airway stenosis. Although percutaneous tracheotomy resulted in a significantly higher rate of postoperative bleeding (6.6%) than the open method (1.9%) (P<.05), the use of outer flange tracheostomy tube sutures may reduce this complication.

OBJECTIVES/HYPOTHESIS: To validate the endonasal surgical approach to frontal sinus in inflammatory sinus disease, trauma, and selective tumor surgery, and to define the role of external approaches to the frontal sinus. Endonasal frontal sinusotomy can range from endoscopic removal of obstructing frontal recess cells or uncinate process to the more complex unilateral or bilateral removal of the frontal sinus floor as described in the Draf II-III drainage procedures. In contrast, the osteoplastic frontal sinusotomy remains the "gold standard" for external approaches to frontal sinus disease. METHODS: A retrospective review of 1286 patients undergoing either endonasal or external frontal sinusotomy by the authors at four university teaching programs from 1977. Prior author reports were updated and previously unreported patient series were combined. RESULTS: Six hundred thirty-five patients underwent type I frontal sinusotomy, 312 type II sinusotomy, and 156 type III sinusotomy. A successful result was seen in these groups, 85.2% to 99.3%, 79% to 93.3%, and 91.5% to 95%, respectively. External frontal sinusotomy or osteoplastic frontal sinusotomy was successfully performed in 187 of 194 patients. Clinical symptoms, endoscopic findings, computed tomography, and magnetic resonance image scanning, and reoperation rate measured postoperative success. CONCLUSIONS: A stepwise approach to the surgical treatment of frontal sinusitis, trauma, and selective benign tumors yields successful results as defined by specific criteria which vary from 79% to 97.8%. The details of specific techniques are discussed, essential points emphasized, and author variations noted.