Decreased retinal sensitivity in depressive disorder: a controlled study.

OBJECTIVE: To compare pupil responses in depressed patients with a seasonal pattern, depressed patients without a seasonal pattern and healthy controls as a function of daylight hours on the testing day. METHOD: Patients suffering from a major depressive episode were included in wintertime. The pupil light reflex was measured at inclusion and in the following summer using a binocular pupillometer. A protocol of low (1 lux) and high (400 lux) intensity red and blue lights was used to assess rod, cone and melanopsin-containing intrinsic photosensitive retinal ganglion cell input to the pupil reflex. RESULTS: The mean group pupil responses associated with a melanopsin-mediated sustained pupil response at 400 lux blue light were significantly reduced in the depressed subjects (N = 39) as compared to the healthy controls (N = 24) (P = 0.023). Across all groups, a reduction in number of daylight hours was significantly associated with a reduction in sustained pupil response (P = 0.007). All groups showed an equal effect of daylight hours on the melanopsin-mediated sustained pupil response. CONCLUSION: The melanopsin-mediated sustained pupil contraction to offset of high-intensity blue light is reduced in depressed patients. These results further emphasize the interaction of light exposure with depression.

Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography.

INTRODUCTION: Optic neuritis causes retinal nerve fiber layer damage, which can be quantified with optical coherence tomography. Optical coherence tomography may be used to track nerve fiber layer changes and to establish a time-dependent relationship between retinal nerve fiber layer thickness and visual function after optic neuritis. METHODS: This prospective case series included 78 patients with optic neuritis, who underwent optical coherence tomography and visual testing over a mean period of 28 months. The main outcome measures included comparing inter-eye differences in retinal nerve fiber layer thickness between clinically affected and non-affected eyes over time; establishing when RNFL thinning stabilized after optic neuritis; and correlating retinal nerve fiber layer thickness and visual function. RESULTS: The earliest significant inter-eye differences manifested 2-months after optic neuritis, in the temporal retinal nerve fiber layer. Inter-eye comparisons revealed significant retinal nerve fiber layer thinning in clinically affected eyes, which persisted for greater than 24 months. Retinal nerve fiber thinning manifested within 6 months and then stabilized from 7 to 12 months after optic neuritis. Regression analyses demonstrated a threshold of nerve fiber layer thickness (75 microm), which predicted visual recovery after optic neuritis. CONCLUSIONS: Retinal nerve fiber layer changes may be tracked and correlated with visual function within 12 months of an optic neuritis event.

Long-term follow-up of idiopathic intracranial hypertension: the Iowa experience.

OBJECTIVE: To evaluate recurrent or delayed worsening of papilledema and visual function in patients with idiopathic intracranial hypertension (IIH) followed for more than 10 years. METHODS: This is an Institutional Review Board approved retrospective chart review of 410 patients with the diagnosis of IIH evaluated at the University of Iowa Hospitals and Clinics from January 1984 to January 1996. Of the 410 patients, 20 patients with IIH who were followed over 10 years at the neuro-ophthalmology clinic met the inclusion criteria. Three neuro-ophthalmologists independently evaluated and graded the visual field examinations and optic disc stereo-photographs for each follow-up visit (median = 15). RESULTS: Of the 20 patients, 11 demonstrated a stable course of disease without worsening in papilledema or visual field, and 9 patients worsened after a stable course. Of these 9 patients, 6 patients experienced delayed worsening (range: 28 to 135 months from presentation) and 3 patients had recurrence after resolution of papilledema 12 to 78 months from initial resolution of the IIH. CONCLUSION: Idiopathic intracranial hypertension is a chronic condition that may worsen after a period of stability, warranting long-term follow-up.

Neural progenitor cell transplants into the developing and mature central nervous system.

When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host-graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal-like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17): PPND family. A longitudinal videotape demonstration.

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), characterized by an autosomal dominant inheritance pattern, has recently been recognized as a distinct entity that can display a confusingly broad clinical phenotype. The pallido-ponto-nigral degeneration (PPND) variant is the prototypical example of the parkinsonism-predominant pattern of FTDP-17. A longitudinal videotape demonstration of the clinical progression of this entity in a single individual, along with brief videotape segments from three additional affected individuals, is presented in order to facilitate recognition of this disorder.

Disorders of the pupil.

The pupil is one objective marker of vision and autonomic pathways. A good understanding of its anatomy and careful examination techniques are the essential tools for proper clinical diagnosis of pupillary disorders.

Comparison of pupil perimetry and visual perimetry in normal eyes: decibel sensitivity and variability.

PURPOSE: To compare the sensitivity and variability of pupil perimetry with visual perimetry at the same retinal locations in normal subjects. METHODS: Pupil perimetry was performed on the right and left eyes of 10 normal subjects using a computerized infrared pupillometer equipped to present perimetric light stimuli and record pupil light reflexes. Eleven locations were tested at different intensities along the horizontal meridian of each eye, and the decibel sensitivity of the pupil light reflex was compared with the visual threshold at the same location. RESULTS: The shape and height of the hill of vision (retinal sensitivity) was very similar between the right and left eyes of each individual using either pupil perimetry (R2 = 0.69) or standard threshold perimetry (R2 = 0.62) but was less similar between subjects. Comparisons between pupil and visual sensitivity revealed a lack of correlation at the same retinal location in normal eyes (R2 = 0.19). CONCLUSIONS: The high intereye correlation for either pupil or visual sensitivity may provide an important tool for detecting focal or asymmetric visual field damage. Although the basic shape of the sensitivity profile of pupil and visual responses was similar under the conditions of testing, the two did not correlate well within each eye among the normal subjects. This highlights that similarities do exist in the sensitivity profile of the two pathways, but they do not seem to vary in the same proportion between normal individuals.

SITA standard in optic neuropathies and hemianopias: a comparison with full threshold testing.

PURPOSE: To compare visual sensitivity, fatigue effect, and probability plot data between Full Threshold (FT) Humphrey automated perimetry and Swedish Interactive Threshold Algorithm (SITA) standard strategies in patients with optic neuropathies and hemianopias. METHODS: Twenty-four patients with nonglaucomatous optic neuropathies and 18 patients with a relative homonymous or bitemporal hemianopia were tested with both conventional perimetry (Humphrey 24-2 program) and "back to back" SITA standard tests (SITA 1, SITA 2) to approximate the test time of the FT test conditions. Also, 28 normal subjects between the ages of 20 and 80 were tested with this protocol. The visual field quadrants with the most damage were used to evaluate any fatigue effect (i.e., possible lack of fatigue effect with SITA standard due to the shorter test time) and to compare probability plot data between FT, SITA 1, and SITA 2. Pointwise total and pattern deviation probability plot defects were weighted by degree of significance and summed. RESULTS: Test times for normal subjects were 45 seconds longer for FT than for the combined test time of SITA 1 + SITA 2. Patients' test times were 40 seconds longer for hemianopias and 90 seconds longer for optic neuropathies with FT than the combined times for two SITA tests. There were higher sensitivities found with SITA 1 compared with Full Threshold (1.06 dB, P< 0.001) and SITA 2 with Full Threshold (0.73 dB, P< 0.001) in the most damaged quadrant for the optic neuropathy patients; for the hemianopia patients the difference in values were between SITA 1 and Full Threshold (0.96 dB, P = 0.07) and between SITA 2 and Full Threshold (0.11 dB, P = 0.87). The second SITA standard test had lower sensitivity than the first SITA standard test by 0.82 dB in hemianopias and by 0.71 dB in optic neuropathy patients. Analysis of the total and pattern deviation probability plot data showed slightly more defects (number and magnitude) with SITA 1 compared to FT for both groups, but the differences were not statistically significant. CONCLUSIONS: Sensitivities were higher in patients with hemianopias or optic neuropathies using SITA standard compared with FT by approximately 1 dB. The probability plot comparison suggests SITA standard is at least as good as FT for detection of visual loss in individual examinations. However, efficacy of SITA standard for serial examinations has not yet been evaluated.

Improvement in papilledema and visual loss after endovascular stent placement in dural sinus thrombosis.

OBJECTIVE: To report two cases of cerebral venous sinus thrombosis with papilledema and visual loss that improved after endovascular stent placement. MATERIALS AND METHODS: Retrospective case series from a tertiary ophthalmic center. RESULTS: Two cases of venous sinus occlusion treated with angioplasty and stenting are described. Both cases experienced improvement in optic disc edema and visual function following the procedures. CONCLUSION: Endovascular stent placement may relieve increased intracranial pressure and papilledema caused by cerebral sinus thrombosis and may prevent further visual loss.

Multifocal electroretinography in multifocal choroiditis and the multiple evanescent white dot syndrome.

PURPOSE: To study and compare the findings on multifocal electroretinography (MERG) between multifocal choroiditis (MFC) and the multiple evanescent white dot syndrome (MEWDS). SUBJECT AND METHODS: Patients were recruited prospectively from the Department of Ophthalmology & Visual Sciences at the University of Iowa Hospitals & Clinics. They were evaluated using Goldmann visual fields (GVF) and MERG. Patients were diagnosed as having either MFC or MEWDS based on their clinical findings before MERG testing. RESULTS: Nineteen patients (23 eyes) were included in the study. Eleven patients were diagnosed with MFC and eight patients with MEWDS. Fourteen eyes with MFC and seven eyes with MEWDS were tested with MERG during the acute phase of their respective conditions. Fourteen patients (8 MFC and 6 MEWDS) were followed serially with MERG. Patients with MEWDS demonstrated focal depression corresponding to GVF defects with subsequent near total recovery of the MERG to baseline. Patients with MFC typically demonstrated diffuse loss of function over the entire test field. Focal scotomata, in addition to the diffuse depression, could be identified in 7 of 14 patients. Patients with MFC demonstrated only partial or no recovery of MERG following acute episodes, which was significantly different from the course followed by patients with MEWDS (P < 0.001, Fisher's exact test). CONCLUSION: Multifocal electroretinography differentiates MFC from MEWDS. Patients with MFC have permanent damage to the retina with diffuse depression of MERG. Patients with MEWDS, however, typically demonstrate greater focal loss initially on MERG followed by nearly full recovery of first order retinal function.

MR imaging of pituitary morphology in idiopathic intracranial hypertension.

The aim of this study was to investigate the morphologic changes of the pituitary gland in patients with the clinical diagnosis of idiopathic intracranial hypertension (IIH). Qualitative and quantitative analyses of pituitary morphology were performed in normal subjects (n = 23), patients with the clinical diagnosis of IIH (n = 40), and patients with acute increased intracranial pressure (AICP; n = 37) caused by acute head trauma. The loss of pituitary height (concavity) on the sagittal T1-weighted image was classified into five categories: I = normal, II = superior concavity that was mild (<(1/3) the height of the sella), III = moderate (between (1/3) and (2/3) concavity of height of sella), IV = severe (>(2/3) concavity of height of sella), and V = empty sella. The area ratio of pituitary gland to sella turcica measured in the midsagittal plane was quantified. Clinical records were retrospectively reviewed to correlate with magnetic resonance (MR) findings. Using moderate concavity (>(1/3)) as the minimum criterion for abnormality, IIH patients had an 85% incidence of morphologic changes with 80% sensitivity and 92% specificity. Empty sella (almost complete concavity of the sella) was found in only 2.5% of patients with IIH. Quantitative analysis of the pituitary gland/sella turcica area ratio showed a significant decrease in patients with IIH (P < 0.0001) but no significant difference between the normal subjects and AICP patients. A posterior deviation of the pituitary stalk was seen in 43% of patients. No enlargement of the ventricles or sulcal effacement was seen in IIH patients. Routine brain MR examination of patients with IIH frequently shows morphologic changes of the pituitary gland ranging from various degrees of concavity to (rarely) the extreme case of an empty sella. The etiology is unknown and may be related to the severity and duration of elevated CSF pressure. Such findings may be useful to facilitate the diagnosis of IIH, particularly in patients with equivocal clinical findings or when IIH is not suspected. J. Magn. Reson. Imaging 2000;12:808-813.

Evaluation of patients with visual field defects following macular hole surgery using multifocal electroretinography.

PURPOSE: To investigate patients with visual field defects following macular hole surgery to determine the cause of such defects, specifically with reference to ischemic damage versus mechanical trauma. METHODS: Five patients with known visual field defects following macular hole surgery were studied with Goldmann perimetry, Humphrey automated perimetry, and multifocal electroretinography (MERG). Three patients returned at a later date for nerve fiber layer analysis. RESULTS: None of the five patients demonstrated evidence of a- or b-wave loss on MERG in the regions corresponding to the visual field defects. Two of three patients studied with the nerve fiber layer analyzer demonstrated significant loss of nerve fiber layer thickness in the quadrant corresponding to the field defect. CONCLUSION: The normal MERG results indicate that the possibility of an arteriolar occlusion as the principal cause for the defects is unlikely in most cases. Data suggest that the site of damage is in the nerve fiber layer, although the specific cause of this damage remains to be determined.

Myositis associated with a Baerveldt glaucoma implant.

PURPOSE: To describe a case of myositis in the presence of a Baerveldt glaucoma implant. METHOD: Case report. RESULTS: A 41-year-old black woman developed myositis after placement of a Baerveldt glaucoma implant. Echography demonstrated migration of the seton plate against the medial rectus muscle insertion. Myositis resolved after removal of the Baerveldt glaucoma implant. CONCLUSION: The Baerveldt glaucoma implant may have precipitated myositis in this patient.

Bacterial conjunctivitis in Muc1 null mice.

PURPOSE: In contrast to wild-type mice, genetically engineered Mucin1 (Muc1) null animals display a marked propensity for development of blepharitis and conjunctivitis. Molecular approaches confirmed the presence of Muc1 mRNA and protein in the conjunctival tissue of wild-type mice and identified the bacterial species in Muc1 null symptomatic mice. METHODS: Muc1 null animals housed in a conventional facility were examined for visually apparent inflammation of the eye and surrounding tissue. Blood taken from overtly affected animals was assayed for antibodies to common murine viral agents. Swabs of infected eyes and whole eye preparations were used to detect and speciate bacterial pathogens. Frozen sections of whole eye, lid margin, and Harderian gland were immunostained with antibodies to Muc1 and cytokeratin 14, both epithelial cell markers. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) were performed on RNA isolated from conjunctiva and Harderian gland of wild-type mice to compare relative levels of transcript. RESULTS: Student's unpaired t-test performed on the eye inflammation frequency of Muc1 null mice confirmed a statistical significance (P < 0.01) when compared to wild-type background animals housed in the same room. Analysis of blood samples from affected Muc1 null animals detected no common murine viral pathogens. Bacterial analysis of conjunctival swabs and whole eye preparations demonstrated the presence of coagulase-negative Staphylococcus, Streptococcus type alpha, and Corynebacterium group G2. Muc1 antibody staining of wild-type sections revealed the presence of Muc1 on conjunctival goblet and non-goblet cells and on the epithelium of the Harderian gland. Serial sections stained with cytokeratin 14 antibody confirmed the epithelial nature of cells expressing the Muc1 protein. RNA from conjunctiva and Harderian gland subjected to RT-PCR and northern blot analysis showed an abundance of Muc1 transcript in these tissues. CONCLUSIONS: Muc1 mRNA and protein are present in murine conjunctival and Harderian gland epithelia. Animals lacking Muc1 mRNA and protein are predisposed to developing eye inflammation when compared to wild-type animals with an intact Muc1 gene. Muc1 appears to play a critical protective role at the ocular surface, presumably by acting as a barrier to infection by certain bacterial strains.

Automated perimetry in amblyopia: a generalized depression.

PURPOSE: To quantitate the visual field abnormalities associated with amblyopia. METHODS: In a prospective study, 37 amblyopic patients (11 anisometropic, 13 strabismic, 9 combination, 4 deprivation) performed automated perimetry in each eye using the Humphrey 30-2 program. Primary outcome measures were foveal threshold, mean deviation, and average threshold. RESULTS: When the probability plots were examined, 21 visual fields in amblyopic eyes were normal, 8 had central scotomas, and 7 had diffuse depressions. No focal defects other than mild central scotomas were seen. However, the foveal threshold of amblyopic eyes was decreased by an average of 7.2 +/- 8.0 dB (P < .0001) compared with fellow eyes; intereye differences in mean deviation (3.2 +/- 5.4 dB; P < .001) and average threshold (2.9 +/- 5.3 dB; P < .005) were also seen. This decrease in sensitivity for the amblyopic eye occurred for all types of amblyopia. The depression in threshold was greatest at the fovea but was detectable and significant at all eccentricities of the 30-degree field. The average threshold in the amblyopic eye was highly correlated with visual acuity (r = .839; P < .001). CONCLUSIONS: Although automated visual fields in amblyopic eyes typically appear normal, all four types of amblyopia are associated with a generalized depression of light sensitivity, which is proportionately greatest at the fovea and highly correlated with visual acuity loss. In general, amblyopia is not associated with any area of focal loss of threshold light sensitivity. If a focal defect is present in the visual field of the amblyopic eye, organic causes of visual loss should be suspected. The Humphrey visual field analyzer STATPAC program (Allergan-Humphrey, Inc, San Leandro, California) may artifactually transform small and generalized full-field depressions in a manner that makes them appear to be isolated central defects.