Steven E. Feldon

Topography of the retinal projection upon the superior colliculus of the cat.

Abstract The distribution of receptive field locations in the visual field was determined for the entire surface of the superior colliculus of anesthetized cats by recording impulse discharges in the superficial layers with microelectrodes. A reconstruction of the visual projection reveals an alinear binocular topography with marked expansion of the representation of the area centralis. At the rostral pole, a small zone displays a separate contralateral projection from the temporla retina (nasal field) containing monocularly excited units with distinctive properties. For the remainder of the colliculus. homonymous points in the visual field for each hemiretina overlap, with a tendency for contralateral dominance. A bilateral projection of the retinal area concerned with central vision may be related to the evolutionary acquisition of an uncrossed optic pathway.

The fellow eye in NAION: Report from the Ischemic Optic neuropathy decompression Trial Follow-up study

PURPOSE To examine the prevalence and incidence of second eye nonarteritic anterior ischemic optic neuropathy (NAION) and associated patient characteristics in patients enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT) Follow-up Study. DESIGN Randomized clinical trial with observational cohort. METHODS Patients randomized to optic nerve sheath decompression surgery or careful follow-up had a diagnosis of acute unilateral NAION, visual acuity between 20/64 and light perception, and were aged 50 years or older. Eligible patients who declined randomization or whose visual acuity was better than 20/64 were not randomized but followed as part of an observational cohort. Follow-up examinations took place at 3, 6, 12, 18, and 24 months and annually thereafter. RESULTS Four hundred eighteen patients were enrolled; 258 randomized and 160 observed. Previous NAION or other optic neuropathy was present in the fellow eye of 21.1% (88/418) of patients at baseline. Four patients developed optic neuropathy in the fellow eye at follow up that could not be conclusively diagnosed as NAION. New NAION in the fellow eye occurred in 14.7% (48/326) of patients at risk during a median follow up of 5.1 years. Randomized patients experienced a higher incidence (35/201; 17.4%) than nonrandomized patients (13/125; 10.4%). A history of diabetes and baseline visual acuity of 20/200 or worse in the study eye, but not age, sex, aspirin use, or smoking were significantly associated with new NAION in the fellow eye. Final fellow eye visual acuity was significantly worse in those patients with new fellow eye NAION whose baseline study eye visual acuity was 20/200 or worse. CONCLUSIONS Follow-up data from the IONDT cohort provide evidence that the incidence of fellow eye NAION is lower than expected: new NAION was diagnosed in 14.7% of IONDT patients over approximately 5 years. Increased incidence is associated with poor baseline visual acuity in the study eye and diabetes, but not age, sex, smoking history, or aspirin use.

Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial.

IMPORTANCE Acetazolamide is commonly used to treat idiopathic intracranial hypertension (IIH), but there is insufficient information to establish an evidence base for its use. OBJECTIVE To determine whether acetazolamide is beneficial in improving vision when added to a low-sodium weight reduction diet in patients with IIH and mild visual loss. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-masked, placebo-controlled study of acetazolamide in 165 participants with IIH and mild visual loss who received a low-sodium weight-reduction diet. Participants were enrolled at 38 academic and private practice sites in North America from March 2010 to November 2012 and followed up for 6 months (last visit in June 2013). All participants met the modified Dandy criteria for IIH and had a perimetric mean deviation (PMD) between -2 dB and -7 dB. The mean age was 29 years and all but 4 participants were women. INTERVENTIONS Low-sodium weight-reduction diet plus the maximally tolerated dosage of acetazolamide (up to 4 g/d) or matching placebo for 6 months. MAIN OUTCOMES AND MEASURES The planned primary outcome variable was the change in PMD from baseline to month 6 in the most affected eye, as measured by Humphrey Field Analyzer. Perimetric mean deviation is a measure of global visual field loss (mean deviation from age-corrected normal values), with a range of 2 to -32 dB; larger negative values indicate greater vision loss. Secondary outcome variables included changes in papilledema grade, quality of life (Visual Function Questionnaire 25 [VFQ-25] and 36-Item Short Form Health Survey), headache disability, and weight at month 6. RESULTS The mean improvement in PMD was greater with acetazolamide (1.43 dB, from -3.53 dB at baseline to -2.10 dB at month 6; n = 86) than with placebo (0.71 dB, from -3.53 dB to -2.82 dB; n = 79); the difference was 0.71 dB (95% CI, 0 to 1.43 dB; P = .050). Mean improvements in papilledema grade (acetazolamide: -1.31, from 2.76 to 1.45; placebo: -0.61, from 2.76 to 2.15; treatment effect, -0.70; 95% CI, -0.99 to -0.41; P < .001) and vision-related quality of life as measured by the National Eye Institute VFQ-25 (acetazolamide: 8.33, from 82.97 to 91.30; placebo: 1.98, from 82.97 to 84.95; treatment effect, 6.35; 95% CI, 2.22 to 10.47; P = .003) and its 10-item neuro-ophthalmic supplement (acetazolamide: 9.82, from 75.45 to 85.27; placebo: 1.59, from 75.45 to 77.04; treatment effect, 8.23; 95% CI, 3.89 to 12.56; P < .001) were also observed with acetazolamide. Participants assigned to acetazolamide also experienced a reduction in weight (acetazolamide: -7.50 kg, from 107.72 kg to 100.22 kg; placebo: -3.45 kg, from 107.72 kg to 104.27 kg; treatment effect, -4.05 kg, 95% CI, -6.27 to -1.83 kg; P < .001). CONCLUSIONS AND RELEVANCE In patients with IIH and mild visual loss, the use of acetazolamide with a low-sodium weight-reduction diet compared with diet alone resulted in modest improvement in visual field function. The clinical importance of this improvement remains to be determined. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01003639.

The Idiopathic Intracranial Hypertension Treatment Trial: Clinical Profile at Baseline

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.

More Than Structural Cells, Fibroblasts Create and Orchestrate the Tumor Microenvironment

The tumor microenvironment comprises many cell types including infiltrating immune cells such as lymphocytes, endothelial cells and a complex stroma consisting mainly of fibroblasts. Fibroblasts are heterogeneous and consist of Thy-1+ and Thy-1− subsets that define different biosynthetic and differentiation potential. They produce mediators linked to carcinogenesis and metastasis, including Cox-2 and PGE2, both of which are also increased in most cancers. This review will highlight the emerging role of the complex fibroblastic stroma in establishing a microenvironment supporting malignant transformation, tumor growth and attenuation of host anti-tumor immune responses.

The epidemiology of giant cell arteritis : a 12-year retrospective study.

OBJECTIVE To study the incidence of biopsy-proven giant cell arteritis (GCA) in a Hispanic population with clinical features suggestive of GCA. DESIGN Retrospective review. PARTICIPANTS Records of 121 consecutive patients who underwent temporal artery biopsy at the Doheny Eye Institute and the Los Angeles County/University of Southern California Hospital from January 1986 through April 1998 were reviewed. MAIN OUTCOME MEASURES The incidence of biopsy-proven GCA was determined, and the biopsy-positive group was compared with the biopsy-negative group. Study variables included age at diagnosis, gender, erythrocyte sedimentation rate (ESR), and ethnic background. RESULTS Among these 121 patients who underwent temporal artery biopsy, the mean age of those in the biopsy-positive group (75.2 +/- 5.0 years) was higher than that of those in the biopsy-negative group (69.1 +/- 9.2 years; P < 0.0001). There was no statistical correlation between biopsy-positive and biopsy-negative groups for gender or ESR level, but ESR was statistically significant for whites when we controlled for race. Nineteen of 66 white patients (29%) had positive biopsy results, whereas only 1 of the 9 Asian patients (11%) none of the 40 Hispanic patients (0%; P < 0.0001) and none of the 6 African American patients (0%) had positive biopsy results. CONCLUSIONS Giant cell arteritis occurs primarily in the white population. None of the Hispanic patients in our study was found to have positive biopsy results. Hispanic persons may have unknown factors that protect them from this disease. Further study is necessary to examine the genetic predisposition.

Age-related deterioration of motion perception and detection

Abstract · Purpose: The purpose of this study was to evaluate the effect of aging on motion detection and perception. · Methods: Forty-six subjects, ages 19–92 years, were asked to view a motion stimulus. Infrared oculography was used to objectively evaluate motion detection by documenting the presence of optokinetic nystagmus as the subjects viewed the stimulus. Subjective responses to motion perception were recorded using a computer joystick. · Results: Optokinetic nystagmus was clearly detectable in all 46 subjects. Motion detection and perception thresholds showed age-related deterioration. No relationship was found to gender or age-gender interaction. · Conclusion: The results indicate motion detection and perception thresholds deteriorate with age. This may reflect a susceptibility to age-related degeneration in specific cortical areas responsible for motion perception as well as neurodegeneration in the retinogeniculate pathway.

Continuous cataplexy in a patient with a midbrain tumor The limp man syndrome

A patient with glioblastoma of the rostral brainstem and hypothalamus exhibited bilateral internuclear ophthalmoplegia and vertical nystagmus; he suffered episodes of cataplexy, narcolepsy, and sleep paralysis. A peculiar fluctuation of posture and tone (“limp man syndrome”) proved to be a manifestation of continuous cataplexy, as documented by H-reflex recordings. This is the first report of a remarkable movement disorder caused by continuous, fluctuating, partial cataplexy, and is the second report of an association between cataplexy and a tumor of the rostral brainstem.

Visual outcomes comparing surgical techniques for management of severe idiopathic intracranial hypertension

OBJECT The object of this study was to compare surgical techniques for management of visual loss in idiopathic intracranial hypertension (IIH) unresponsive to medical treatment. METHODS The published literature was reviewed using electronic and manual search techniques. Articles were categorized based upon the surgical procedure performed, including optic nerve sheath decompression (ONSD), also called optic nerve sheath fenestration; intracranial venous sinus stent placement; ventriculoperitoneal (VP) shunt placement; and lumboperitoneal (LP) shunt placement. Demographic data and visual outcome of the cumulative experience were compiled and compared for each type of surgical intervention. RESULTS Seventeen patients treated by stent placement, 31 by VP shunt placement, 44 by LP shunt placement, and 252 patients by ONSD were identified in the literature; average follow-up ranged from 11.8 months for patients treated with stents to 57.2 months for those treated with LP shunts. Improved or resolved vision deficit was noted in 38.7% of patients after VP shunt placement, 47% of patients after stent placement, 44.6% of patients after LP shunt placement, and 80% of eyes after ONSD. Visual worsening was rare for all procedures evaluated. CONCLUSIONS There is a paucity of information regarding visual outcomes from intracranial venous stent placement and cerebrospinal fluid diversion procedures. Visual outcomes from ONSD are better documented and appear to be superior to other surgical techniques for management of IIH. Further studies with improved data collection regarding visual outcomes are needed for surgical procedures other than ONSD in order to assess their possible value as treatments for visual loss in IIH.

Graves Exophthalmos Unrelated to Extraocular Muscle Enlargement: Superior Rectus Muscle Inflammation May Induce Venous Obstruction

Exophthalmos is the most commonly measured sign of Graves ophthalmopathy, whereas enlargement of the extraocular muscles is the principal pathologic abnormality. The purpose of this article is to explore possible etiologies of increased volume of orbital fat and of proptosis in patients with no substantially increased total extraocular muscle volume. Computed tomographic scans of the 13 orbits reviewed in this study had the following characteristics in common: a fine, reticular pattern within the orbital fat, a prominent superior ophthalmic vein, and an enlarged superior rectus muscle. Quantitative analysis revealed that superior rectus muscle volume showed a statistically significant correlation with proptosis, whereas medial, lateral, and inferior rectus muscle volumes did not correlate with proptosis. Based on anatomic considerations, the authors postulate that superior rectus muscle enlargement alone may produce reduced venous outflow from the orbit, thereby expanding the apparent orbital fat volume and producing proptosis.