Ronald M. Burde

Ophthalmologic Examination of Patients With Seasonal Affective Disorder, Before and After Bright Light Therapy

PURPOSE We assessed the potential ocular hazards of bright light therapy for patients with seasonal affective disorder, after both short- and long-term treatment, and identified prospective patients with pre-existing ocular abnormalities. METHODS Fifty patients with seasonal affective disorder received daily exposure to artificial light in the morning or evening for 30 minutes at an illuminance level of 10,000 lux (irradiant dose, 0.016 J/cm2). Ophthalmologic examinations were performed before and after short-term treatment (two to eight weeks) and after three to six years of use during the fall and winter months. Over the four years of patient intake, the eye examination included subsets of the following tests: visual acuity, intraocular pressure, slit-lamp biomicroscopy, direct and indirect ophthalmoscopy, color vision, visual field, fundus photography, Amsler grid, ocular motility, pupillary reactions, contrast sensitivity, stereopsis, and the macular stress test. RESULTS No ocular changes were detected after short-term treatment. Long-term treatment (three to six years) of 17 patients, with cumulative exposure durations of 60 to 1,250 hours, also resulted in no ocular abnormalities. CONCLUSIONS Light therapy yields about 75% clinical remissions. It is effective as an antidepressant and appears safe for the eyes. Current knowledge is insufficient to specify any definite ocular contraindications for bright light therapy, although we recommend that patients with preexisting ocular abnormalities and those using photosensitizing drugs undergo treatment only with periodic ophthalmologic examination.

Long-term follow-up and recent observations on 305 cases of orbital decompression for dysthyroid orbitopathy

Dysthyroid exophthalmopathy (orbitopathy) results from an enlargement of extraglobal orbital structures, producing ocular proptosis, optic nerve compression, and corneal exposure. Treatment with corticosteroids and radiation may be beneficial; refractory cases require surgical decompression of the orbit. Transantral orbital decompression was described by Walsh and Ogura and has been performed in over 350 patients at this institution. A review of 305 patients with long‐term follow‐up was performed. Visual acuity improved or was maintained ut preoperative levels in over 95% of the patients, with ocular recession ranging from 1 to 12 mm (average: 4 mm). Postoperative ocular balance of relative exophthalmos was to within 1 mm in 76% of the patients and to within 2 mm in approximately 90% of the patients. Normal postoperative extraocular muscle balance was present in 99 patients. Immediate postoperative diplopia was noted in 206 patients. Long‐term follow‐up revealed that in 137 of these patients, diplopia resolved or responded to conservative management. Extraocular muscle surgery was required for correction in 69 patients. Twenty‐seven patients had postoperative complications. These included 16 patients with hypesthesia of the infraorbital nerve, 5 patients with sinusitis, 3 patients who had incomplete decompression, 2 patients with oral antral fistulae, and 1 patient who had CSF rhinorrhea. Five patients, despite surgery, radiation, and steroid therapy progressed to blindness. We conclude that this procedure is effective and carries few complications. Orbital imaging, using computed tomography or magnetic resonance sequence with reconstructive capabilities, permits early diagnosis and treatment of dysthyroid compression optic neuropathy.

Visual Field Defects in Idiopathic Intracranial Hypertension (Pseudotumor Cerebri)

Idiopathic intracranial hypertension (pseudotumor cerebri) produces loss of visual field and visual acuity. We conducted a retrospective study of 12 patients (all female, ranging in age from 6 to 44 years) using computerized visual field analysis. In seven of the 12 patients, the visual field loss appeared to be permanent, and follow-up was too short for the final outcome to be determined in two others. The visual field defects were those known to be associated with optic disk lesions. The most common were blind spot enlargement (all 12 cases), isopter constriction (nine cases), and loss on the nasal side of the visual field (seven cases), especially in the inferonasal quadrant. Four patients had diminished visual acuities. The reversibility of the visual field defects was correlated with the presence (nonreversible) or absence (reversible) of ophthalmoscopic signs of chronic papilledema. Because visual loss is reversible if treatment is begun before the onset of the optic disk changes associated with chronic papilledema, patients with idiopathic intracranial hypertension should be monitored carefully with frequent perimetric and visual acuity testing.

Fascicular Arrangement in Partial Oculomotor Paresis

We treated two patients with partial oculomotor paresis who had pupillary mydriasis, marked inferior rectus muscle weakness, and medial rectus muscle paresis, which were attributed to an ipsilateral fascicular lesion, demonstrated on neuroimaging studies. These cases support the fascicular proximity of inferior rectus muscle and pupillary fibers and suggest that fascicular medial rectus and inferior rectus muscle fibers are adjacent to each other.

Brainstem connections to the Edinger-Westphal nucleus of the cat: a retrograde tracer study

Although the pupillary system has been under investigation for more than a century, there still remains uncertainty as to the anatomical pathways which subserve the afferent and efferent limbs of the light reflex. Part of this uncertainty is due to the fact that the oculomotor parasympathetic preganglionic neurons are not confined to the Edinge~Westphal (EW) nucleus, but are also found dorsal and ventral to the oculomotor nucleus in the cat 4.7.8. Graybiel and Hartweig 2 elucidate some of the afferent connections to the oculomotor complex with the horseradish peroxidase technique. They find labeling in the interstitial nucleus of Cajal, nucleus of the posterior commissure, abducens nucleus, areas equivalent to the A5 and A7 catecholamine cell groups, superior and medial vestibular nuclei, nucleus prepositus hypoglossi, and r/ucleus intercalatus. Unfortunately, their study does not detect any potential differences with regard to the inputs to the somatic and visceral outflows of the oculomotor nucleus. The present study is designed to determine the afferent connections of the region of the pupilloconstrictor nucleus of the cat. Fifteen adult cats were anesthetized with sodium pentobarbital (35 mg/kg) and placed in a stereotaxic surgical frame. Injections of 0.4 ~1 of 3% Fast Blue dissolved in distilled water were made with a 5/~1 Hamilton syringe over 20 min into the region of the EW nucleus. The cats were given benzothane penicillin (400,000 units) and allowed to survive 3 days. Then they were reanesthetized and perfused with 0.9% saline, followed by 10% formalin in 0.1 M phosphate buffer (pH 7.4), and 10% formalin-30% sucrose in 0.1 M phosphate buffer (pH 7.4). The brain was removed and the brainstem blocked for immediate sectioning on a freezing microtome. Transverse serial sections (40/tm) were cut, collected and washed in phosphate buffer, mounted on glass slides and air dried. The material was analyzed using a fluorescence microscope. Camera lucida drawings were made of every sixth section. The results of one of the representative experiments in which an injection was made in the region of the EW nucleus are shown in Fig. 1. This injection involved the area ventral to the oculomotor nucleus which contains the largest number of oculomotor parasympathetic preganglionic neurons ~.7-8. Retrogradely labeled cells were found in the olivary and medial pretectal nuclei, nucleus of the posterior commissure, interstitial nucleus of Cajal, nucleus of Darkschewitsch, ventral tegmental area, and reticular division of

Treatment of temporal arteritis with ocular involvement

A 78-year-old white woman had catastrophic visual loss in one eye due to temporal arteritis. Despite treatment with doses of oral corticosteroids high enough to normalize the Westergren erythrocyte sedimentation rate, she experienced progressive retinal ischemia with visual loss in the second eye. The use of 1,000 mg of pulsed intravenous methylprednisolone every 12 hours restored her vision. Brief hospitalization of patients with arteritic ischemic optic neuropathy for treatment with intravenous methylprednisolone may offer a significant chance of visual recovery of the involved eye and provide optimal protection to the uninvolved eye.

Cyclin D- and E-Dependent Kinases and the p57 KIP2 Inhibitor: Cooperative Interactions In Vivo

ABSTRACT This study examines in vivo the role and functional interrelationships of components regulating exit from the G1 resting phase into the DNA synthetic (S) phase of the cell cycle. Our approach made use of several key experimental attributes of the developing mouse lens, namely its strong dependence on pRb in maintenance of the postmitotic state, the down-regulation of cyclins D and E and up-regulation of the p57 KIP2 inhibitor in the postmitotic lens fiber cell compartment, and the ability to target transgene expression to this compartment. These attributes provide an ideal in vivo context in which to examine the consequences of forced cyclin expression and/or of loss of p57 KIP2 inhibitor function in a cellular compartment that permits an accurate quantitation of cellular proliferation and apoptosis rates in situ. Here, we demonstrate that, despite substantial overlap in cyclin transgene expression levels, D-type and E cyclins exhibited clear functional differences in promoting entry into S phase. In general, forced expression of the D-type cyclins was more efficient than cyclin E in driving lens fiber cells into S phase. In the case of cyclins D1 and D2, ectopic proliferation required their enhanced nuclear localization through CDK4 coexpression. High nuclear levels of cyclin E and CDK2, while not sufficient to promote efficient exit from G1, did act synergistically with ectopic cyclin D/CDK4. The functional differences between D-type and E cyclins was most evident in the p57 KIP2 -deficient lens wherein cyclin D overexpression induced a rate of proliferation equivalent to that of the pRb null lens, while overexpression of cyclin E did not increase the rate of proliferation over that induced by the loss of p57 KIP2 function. These in vivo analyses provide strong biological support for the prevailing view that the antecedent actions of cyclin D/CDK4 act cooperatively with cyclin E/CDK2 and antagonistically with p57 KIP2 to regulate the G1/S transition in a cell type highly dependent upon pRb.

Visual Recovery in Two Patients after Intravenous Methylprednisolone Treatment of Central Retinal Artery Occlusion Secondary to Giant-cell Arteries

Two patients with central retinal artery occlusions secondary to biopsy-proven giant-cell arteritis lost visual acuity to no light perception but recovered to baseline acuity after treatment with intravenous methylprednisolone at a dose of 15 to 30 mg/kg/day. The potential advantages and theoretical basis of early and aggressive treatment with large-dose intravenous corticosteroids in arteritic central retinal artery occlusion are discussed.

Visual parameters associated with recovered retrobulbar optic neuritis.

Visual acuity, color vision, pupillary reaction, induced Pulfrich phenomenon, kinetic fields, static fields, afterimage testing, and ophthalmoscopic evaluation were studied in nine patients with a history of retrobulbar neuritis. The most consistently reliable test for determining the presence of an old optic nerve defect in these patients was meridional 0 to 180 degrees static perimetry. There was a uniform decrease in brightness discrimination to either side of the foveal peak.

Three-Dimensional Topography of the Central Visual Field: Sparing of Foveal Sensitivity in Macular Disease

Threshold static perimetry was performed using test object patterns that covered contiguous areas of the central visual field. Computer imaging methods were used to display a three-dimensional surface that was interpolated between the sensitivity values at each of the test object locations. The examinations covered the area out to and including 10 degrees of eccentricity from the point of fixation, corresponding to the same area of the visual field covered by the Amsler grid. The normal visual field surface appears as a high plateau with a smoothly rising level of sensitivity forming a peak at the point of fixation. It was found that in a variety of macular diseases, including those caused by vascular, as well as primary degenerative disorders, central scotomas were characterized by relative sparing of visual sensitivity at the point of fixation. The pattern thus produced was one of a ring-shaped depression within the central 10 degrees of the visual field. This phenomenon was present in 20% of cases with central scotomas resulting from macular disease, but was not found in any eye of 64 patients suffering from central scotomas as a result of optic nerve disease. This pattern of visual field loss may be common, though not frequently recognized. It is proposed that the phenomenon of preservation of foveal sensitivity may be a marker for macular disease, as distinct from central visual field defects arising from optic nerve disease.