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.

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.

Brief, transient Horner's syndrome can be the hallmark of a carotid artery dissection.

We describe a 41-year-old woman in whom the diagnosis of carotid artery dissection was suspected based on a recent history of anisocoria and ipsilateral ptosis that lasted 2 days. She had a normal neurologic examination, including no clinical evidence of anisocoria or ptosis. Subsequently, a cocaine test demonstrated pharmacologic Horner's syndrome. MRI confirmed the carotid dissection. This patient illustrates that a history of transient pupillary and eyelid abnormalities can lead to the diagnosis of a carotid dissection. Specific questioning about transient anisocoria and ptosis should be considered when a carotid artery dissection is suspected. Pharmacologic testing may be a useful tool in such instances.

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.

Mae III positively detects the mitochondrial mutation associated with type I Leber's hereditary optic neuropathy.

Leber's hereditary optic neuropathy is a blinding disease that usually causes acute or subacute central visual loss in adolescent and young adult males. In patients who lack a family history of a similar illness, Leber's disease has been a diagnosis of exclusion. The recent discovery of a specific mitochondrial mutation in many pedigrees affected with the disease has provided the basis for rapid molecular diagnosis of one genetic type of Leber's disease. We have developed a new method, based on a Mae III (Boehringer Mannheim Biochemicals, Indianapolis, Ind) restriction fragment length polymorphism, for detecting the Wallace-type Leber's mutation. The method has several advantages over the previously used SfaN I method that make it more suitable for use as a general laboratory test. We demonstrate the utility of this new test in the diagnosis of Leber's disease in a patient with no family history of visual loss.

Acepromazine. Effects on intraocular pressure.

We investigated the effects of the topical application of acepromazine maleate on the intraocular pressure (IOP) in 27 adult rhesus monkeys. The monkeys were divided into two groups: group 1 (16 monkeys) had both eyes normal, and group 2 (11 monkeys) had experimental chronic glaucoma in one eye and a normal fellow eye. One drop of 1% acepromazine maleate solution was instilled in one eye of monkeys in group 1 and in the glaucomatous eye of monkeys in group 2; the other eye served as the control. The IOP was measured before drug administration and 1, 4, 8, 24, and 32 hours after, with detailed slit-lamp examination of the anterior segment. Acepromazine produced no change in IOP in eyes in group 1, but it produced a fall in pressure in all eyes with high IOP in group 2, evident 1 hour after instillation, maximal between 4 and 8 hours, and still remaining after 32 hours. The pupil showed no change in size, but a transient ptosis was observed in the treated eye in all monkeys.

Critical evaluation of the cocaine test in the diagnosis of Horner's syndrome.

We evaluated the effectiveness of the cocaine test for diagnosing Horner's syndrome. The test was administered to 119 patients with a diagnosis of Horner's syndrome and to 50 normal subjects. We compared the cocaine-induced anisocoria in the two groups by measuring photographs of the pupils. We found the cocaine test to be highly effective in separating normal subjects from patients with Horner's syndrome. The chances of having Horner's syndrome increased with the amount of cocaine-induced anisocoria. Through the use of logistic regression analysis, we determined the odds ratio of having Horner's syndrome compared with not having it for each 0.1-mm increment of anisocoria measured after cocaine administration. A postcocaine anisocoria value of 0.8 mm gave a mean odds ratio of approximately 1050:1 that Horner's syndrome was present (lower 95% confidence limit = 37:1). We found that simply measuring the postcocaine anisocoria provided a better prediction of Horner's syndrome than taking the trouble to calculate the net change in anisocoria. Odds ratios should help the clinician decide if the result of a cocaine test is indicative of Horner's syndrome.

Long-term fluctuation of relative afferent pupillary defect in subjects with normal visual function.

PURPOSE: To determine whether the relative afferent pupillary defect (RAPD) remains constant over time in normal subjects. METHODS: Seventeen normal subjects were tested with infrared pupillography and automated perimetry in four sessions over 3 years. The changes in RAPD and visual field asymmetry between testing sessions were compared. RESULTS: The range of RAPD was 0.0 to 0.3 log unit, and the difference in the mean deviation between the eyes on automated static perimetry was 0 to 3 dB. Eight subjects repeatedly had an RAPD in the same eye. There was no correlation between the RAPD and the visual field asymmetry at the same visit. Changes in the magnitude of the RAPD between any two sessions were typically small (median, 0.08 log unit; 25th percentile, 0.04 log unit; 75th percentile, 0.15 log unit). CONCLUSIONS: Some normal subjects may show a persistent but small RAPD in the absence of detectable pathologic disease. Therefore, an isolated RAPD in the range of 0.3 log unit that is not associated with any other significant historical or clinical finding should probably be considered benign.

Variability of the relative afferent pupillary defect.

PURPOSE: Afferent asymmetry of visual function is detectable in both normal and pathologic conditions. With a computerized test, we assessed the variability in measuring afferent asymmetry of the pupillary light reflex, that is, the relative afferent pupillary defect. METHODS: In ten normal subjects, pupillary responses to an alternating light stimulus were recorded with computerized infrared pupillography. The relative afferent pupillary defect for each test was determined by using a new computer analysis. The 95% confidence interval of each determination of relative afferent pupillary defect was used to represent the short-term fluctuation in its measurement. To optimize the test for clinical use, we studied the influence of stimulus intensity, duration, and number on the variability of the relative afferent pupillary defect. RESULTS: When the relative afferent pupillary defect was based on only a few light alternations (stimulus pairs), there was excessive variability in its measurement (95% confidence interval > 0.5 log units). With approximately 200 stimulus pairs, the 95% confidence interval was reduced to less than 0.1 log unit (relative afferent pupillary defect +/- 0.05 log unit). Also, there was less variability when the dark interval between alternating light stimulation was less than one second. CONCLUSIONS: Computerized infrared pupillography can standardize the alternating light test and minimize the error in quantifying a relative afferent pupillary defect. A reproducible relative afferent pupillary defect measurement is desirable for defining afferent injury and following the course of disease.

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.

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.

The relationship between static perimetry and the relative afferent pupillary defect.

This study was undertaken to understand better how damage to the anterior visual pathway may affect the relationship between the visual and pupillomotor systems. The relative afferent pupillary defect and the interocular difference in visual field mean deviation (determined by the Humphrey Field Analyzer Statpac program) were correlated in 137 patients. A moderate linear correlation (r = .66) was found. In 25 patients tested by both static and kinetic perimetry, the correlation could not be significantly improved by considering field loss outside of 30 degrees. The correlation was further studied in four subcategories of diagnosis: optic neuritis (n = 36), idiopathic intracranial hypertension (n = 26), compressive optic neuropathy (n = 14), and anterior ischemic optic neuropathy (n = 7). In compressive optic neuropathy and idiopathic intracranial hypertension, the difference in mean deviation between the two eyes was associated with a larger relative afferent pupillary defect than in optic neuritis and anterior ischemic optic neuropathy. In optic neuritis, the correlation was the poorest. These results indicate that diseases of the afferent visual system may not necessarily affect visual threshold (as tested by static perimetry) and the pupillary light reflex (a suprathreshold test) in the same way.

Hourglass-shaped visual fields as a sign of bilateral lateral geniculate myelinolysis.

PURPOSE/METHODS: Bilateral visual field defects resembling an hourglass could be produced by bilateral lateral geniculate lesions. We recently encountered such deficits in a 37-year-old woman after an episode of central pontine myelinolysis. RESULTS/CONCLUSIONS: Automated static perimetry demonstrated the congruous visual field defects to involve both halves of the visual field. They were confirmed with kinetic perimetry, and they remained stable for four years. Magnetic resonance imaging demonstrated enhancing lesions characteristic of myelinolysis in each lateral geniculate.

Palpebral fissure responses to topical adrenergic drugs.

We measured the magnitude and time course of the increase in palpebral fissure width in ten normal volunteers in response to direct-acting (2.5% phenylephrine, 1% apraclonidine) and indirect-acting (10% cocaine, 1% hydroxyamphetamine) topical adrenergic drugs given in one eye. The increase in the palpebral fissure width of the treated eye was compared to the width of the untreated, control eye during a period of 60 minutes after each drug was administered. The difference in fissure width (asymmetry) between the treated and untreated eyes increased significantly for all drugs during the three- to 60-minute time period after treatment. There was no significant difference in the maximum eyelid effect among the adrenergic drugs tested. The drugs exerted their maximum effect by 30 minutes in 39 of the 40 trials (97.5%). The direct-acting drugs tended to exert their effect more quickly than the indirect-acting drugs. Our results demonstrate the expected increase in palpebral fissure width in response to topical adrenergic drugs in normal eyes. This information will provide a basis for evaluating Müller's muscle and its sympathetic innervation in patients with blepharoptosis.

Hydroxyamphetamine mydriasis in normal subjects.

Hydroxyamphetamine eyedrops are used to help localize the lesion in Horner's syndrome. Because normal variability in the response to the eyedrops may influence the interpretation of test results in patients with Horner's syndrome, we studied both the interocular variability of the drug's mydriatic effect within each normal subject and the variation between individuals. We used photographs to document the variability among 26 normal subjects. Hydroxyamphetamine hydrobromide 1% eyedrops (Paredrine) were placed in both eyes of normal subjects in the same way that patients with Horner's syndrome are tested. The drug produced a mean increase in pupil size of 1.96 mm (+/- 0.61 S.D.) in the 52 eyes tested. In normal subjects, the mydriatic effect of hydroxyamphetamine was symmetric in each pair of eyes. The mean interocular asymmetry of mydriasis as measured by the difference in dilation (right eye dilation minus left eye dilation) was -0.087 mm (+/- 0.29 S.D.). Thus, the variability of hydroxyamphetamine mydriasis from one eye to the other in a single subject was much lower than the variability between subjects.

Hydroxyamphetamine mydriasis in Horner's syndrome.

We studied hydroxyamphetamine hydrobromide 1% (Paredrine) mydriasis in 54 patients with Horner's syndrome to determine its effectiveness in distinguishing preganglionic lesions from postganglionic lesions. The difference in pupillary dilation between the unaffected and affected sides was used as a measure of the hydroxyamphetamine effect. We found that patients who had clinical evidence of damage to the postganglionic neuron of the oculosympathetic pathway had less pupillary dilation on the affected side. In contrast, almost all patients judged to have clinical evidence of preganglionic lesions dilated more on the affected side. We determined the probability that a given difference in pupillary dilation between the involved and uninvolved side is the result of a postganglionic lesion.

Autoimmune retinopathy in the absence of cancer.

PURPOSE: To report the clinical and immunologic features of two patients with progressive retinal degeneration and circulating antiretinal antibodies without systemic malignancy. METHODS: Two patients were followed up for 5 to 7 years. Comprehensive medical and ophthalmic examinations and visual function testing included manual perimetry and standardized electroretinography. Patient sera were tested for antiretinal antibodies by Western blot and immunoperoxidase indirect cytochemistry techniques. RESULTS: Two patients had family history of autoimmune disease. Each had severe monocular visual loss with photopsia, a ring scotoma, and abnormal electroretinogram despite a normal-appearing ocular fundus. One had a flat electroretinogram; the other had inner retina dysfunction, with selective b wave loss and abnormal oscillatory potentials. Both patients' sera had antiretinal antibodies that specifically labeled the inner plexiform layer of donor retina by indirect immunoperoxidase testing. Neither had any sign of cancer. CONCLUSIONS: In two patients without systemic malignancy, the symptoms, perimetric findings, and normal fundus appearance resembled cancer associated retinopathy. Electroretinography and antibody findings indicating dysfunction of the inner retina are distinct from those of cancer-associated retinopathy. These two cases raise the possibility of an autoimmune mechanism for retinal degeneration that is not cancer associated. Further study is necessary to determine the role of antiretinal antibodies in these patients.

Bilateral central ptosis in acquired immunodeficiency syndrome.

A man with acquired immune deficiency syndrome suddenly developed bilateral complete ptosis and minor vertical gaze limitation. Magnetic resonance imaging revealed a lesion in the midbrain surrounding the sylvian aqueduct in addition to bilateral masses in the caudate nuclei. Pathologic examination showed that the caudate lesions were central nervous system lymphoma of B cell origin, but the midbrain lesion contained only signs of AIDS encephalopathy. The periaqueductal lesion involved the caudal central subnucleus and probably also the subnuclei of the superior and inferior recti of the oculomotor nuclear complex bilaterally.

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.