Diagnosing Optic Disc Drusen in the Modern Imaging Era: A Practical Approach.

Optic disc drusen (ODD) are a well-recognised cause of an elevated optic disc appearance. When visible with ophthalmoscopy and fundus photography, ODD are readily identified. Yet, in more subtle cases of ODD, ancillary testing may be needed to render the diagnosis. Facilitating the diagnosis of ODD has clinical relevance, because affected individuals may otherwise undergo unnecessary costly and invasive investigations to rule out raised intracranial pressure and other causes of optic disc oedema. In this review, the role of established and emerging optical coherence tomography (OCT) techniques in the diagnosis and management of ODD cases is reviewed. A practical approach is taken to explain how to optimise use of commercially available OCT technology in the clinical setting. Optical coherence tomography provides many advantages over other imaging modalities in the diagnosis of ODD, including the ability to correlate retinal measures of neuroaxonal structure with drusen characteristics. Earlier spectral domain OCT techniques, however, were hindered by poor penetrance. In the modern imaging era, enhanced depth imaging OCT and swept source OCT enable higher resolution of ODD and other optic nerve head structures that might otherwise be mistaken for drusen. Ongoing studies featuring OCT angiography indicate that this technique may provide complementary information about microvascular supply that correlate with structural measures of optic nerve injury. Advances in OCT will continue to improve diagnostic accuracy and inform clinical understanding regarding structure-function correlations germane to the longitudinal follow up of ODD patients.

Not looking while leaping: the linkage of blinking and saccadic gaze shifts.

Many vertebrates generate blinks as a component of saccadic gaze shifts. We investigated the nature of this linkage between saccades and blinking in normal humans. Activation of the orbicularis oculi, the lid closing muscle, EMG occurred with 97% of saccadic gaze shifts larger than 33 degrees. The blinks typically began simultaneously with the initiation of head and/or eye movement. To minimize the possibility that the blinks accompanying saccadic gaze shifts were reflex blinks evoked by the wind rushing across the cornea and eye-lashes as the head and eyes turned, the subjects made saccadic head turns with their eyes closed. In this condition, orbicularis oculi EMG activity occurred with all head turns greater than 17 degrees in amplitude and the EMG activity began an average of 39.3 ms before the start of the head movement. Thus, one component of the command for large saccadic gaze shifts appears to be a blink. We call these blinks gaze-evoked blinks. The linkage between saccadic gaze shifts and blinking is reciprocal. Evoking a reflex blink prior to initiating a voluntary saccadic gaze shift dramatically reduces the latency of the initiation of the head movement.

Parainfectious optic neuritis and encephalomyelitis. A report of two cases with thalamic involvement.

Two children developed mental status alteration and bilateral profound visual loss secondary to optic neuritis. The clinical picture was consistent with parainfectious encephalomyelitis. Magnetic resonance imaging showed bilateral involvement of the thalamus in both cases. In one case the thalamic involvement was solitary and was suspected initially to represent a primary thalamic neoplasm. This was ruled out by a stereotactic biopsy of the thalamus, which showed perivascular inflammation consistent with parainfectious encephalomyelitis. The clinical and neuroimaging findings improved significantly following corticosteroid administration. Several relapses occurred upon initial attempts at corticosteroid cessation.

A role for the basal ganglia in nicotinic modulation of the blink reflex.

In humans and rats we found that nicotine transiently modifies the blink reflex. For blinks elicited by stimulation of the supraorbital branch of the trigeminal nerve, nicotine decreased the magnitude of the orbicularis oculi electromyogram (OOemg) and increased the latency of only the long-latency (R2) component. For blinks elicited by electrical stimulation of the cornea, nicotine decreased the magnitude and increased the latency of the single component of OOemg response. Since nicotine modified only one component of the supraorbitally elicited blink reflex, nicotine must act primarily on the central nervous system rather than at the muscle. The effects of nicotine could be caused by direct action on lower brainstem interneurons or indirectly by modulating descending systems impinging on blink interneurons. Since precollicular decerebration eliminated nicotine's effects on the blink reflex, nicotine must act through descending systems. Three lines of evidence suggest that nicotine affects the blink reflex through the basal ganglia by causing dopamine release in the striatum. First, stimulation of the substantia nigra mimicked the effects of nicotine on the blink reflex. Second, haloperidol, a dopamine (D2) receptor antagonist, blocked the effect of nicotine on the blink reflex. Third, apomorphine, a D2 receptor agonist, mimicked the effects of nicotine on the blink reflex.

Eyelid movements in facial paralysis.

We studied the eyelid movements of six patients with unilateral, isolated, facial paralysis using the magnetic search coil. The most significant abnormality consisted of a reduction in the magnitude of the orbicularis oculi contraction with slowing of the peak velocity of the closing phase of the blink. The closing phase blink velocity, which normally increases linearly as a function of amplitude (main sequence), in our patients displayed a relationship characterized by a slow saturating power function that fell off the main sequence. The contralateral normal lid in some cases can show adaptive signs of hyperactivity during the closing phase of the blink. Lid saccades showed a small but consistent decrease in amplitude and velocity compared with the contralateral unaffected eyelid. Unlike the closing phase of the blink, peak velocities of lid saccades stayed on the main sequence. In this study, we discuss how the eyelid executes downward lid saccades based purely on a passive mechanism.

Eyelid movements. Mechanisms and normal data.

This study provides a comprehensive description of upper eyelid movement in normal human subjects. Using the magnetic search coil technique to monitor lid position and modified skin electrodes to record orbicularis oculi electromyographic (EMG) activity, the authors found that the basic eyelid movements, blinks, and saccadic lid movements, can be uniquely and reliably characterized by their amplitude-maximum velocity relationships. The data show that similar increases in levator palpebrae activity produce the upward lid movements that accompany upward saccadic eye movements as well as the upward phase of a blink. The lid movements that accompany downward saccadic eye movements arise almost exclusively from the passive downward forces and relaxation of the levator palpebrae muscle. In contrast, active orbicularis oculi contraction and the passive downward forces act together to generate lid closure with a blink. These normative data and techniques provide the basis for the clinical analysis of lid motility by which abnormal lid movements can be compared with normal lid kinematics.

Eyelid movements before and after botulinum therapy in patients with lid spasm.

Quantitative analysis of lid motility is presented for 4 individuals with hemifacial spasm and 1 with Meige's syndrome. The data were obtained, by means of a magnetic search coil technique, prior to and 1 week after injection of botulinum toxin into the orbicularis oculi muscle. Before treatment, the peak velocity of blink-related lid lowering and lid raising was slower than normal, yet lid saccades were normal. After botulinum treatment, significant decreases occurred in (1) the amplitude of blinks and lid saccades, and (2) the peak velocity of the blink down-phase. Botulinum treatment significantly alters blink lid-lowering kinematics, while saccadic lid-lowering kinematics are normal, providing further evidence that the orbicularis oculi muscle does not play a primary role in downward lid saccades.

Posterior scleritis as an intraocular tumour.

Posterior scleritis rarely presents as a large 'intraocular tumour' and continues to be a challenge in diagnosis and management. We present the case of a 66-year-old male with no known rheumatic disease, pain, proptosis, or diplopia, but with progressively decreasing visual acuity and a large, discrete 'subretinal tumour', 15 X 17 mm basal diameter and 8.3 mm apical height. Histologically the tumour was shown to be grossly thickened and necrotic sclera.

Electrophoresis combined with immunologic identification of human tear proteins.

The protein content of normal human tears from five subjects was examined by molecular weight separation using SDS-polyacrylamide gel electrophoresis (PAGE) and by charge separation using agarose isoelectric focusing (IEF) gels. After separation, specific proteins were identified by immunoblot and immunofixation. Tear proteins examined included albumin, IgA, IgG, prealbumin, lactoferrin, lysozyme, secretory component and transferrin. These techniques required 1 to 14 microliters unconcentrated tears. We found SDS-PAGE superior to agarose IEF to examine total tear protein pattern, and silver stain almost ten-fold more sensitive than Coomassie blue stain. Immunologic staining markedly enhanced protein detection in all tear samples and appeared to offer the definitive method to probe for a specific protein in tears. In this study prealbumin and a portion of the IgG were present in normal tears at higher than expected molecular weight, suggesting they were present in complexed form. Prealbumin and secretory component staining showed marked variability between subjects. These techniques should be applicable to examine tear proteins in a variety of ocular disease states.

Neuropeptides and the innervation of the avian lacrimal gland.

The chicken Harderian gland, the major lacrimal gland, has two major cell populations: a cortical secretory epithelium and a medullary interstitial cell population of lymphoid cells. There is an extensive acetylcholinesterase (AChE) network throughout the gland, as well as catecholamine positive fibers among the interstitial cells. There are substance P-like (SPLI) and vasoactive intestinal polypeptide-like (VIPLI) immunoreactive fibers throughout the gland. These fibers are particularly dense and varicose among the interstitial cells. The adjacent pterygopalatine ganglion complex has neuronal somata that exhibit VIPLI and were AChE-positive. This ganglion complex also contains SPLI and catecholamine-positive fibers. In regions of the ganglion, the somata appear surrounded by SPLI varicosities. Surgical ablation of the ganglion eliminated or reduced the VIPLI, AChE and catecholamine staining in the gland. The SPLI was reduced only in some regions. Ablation of the superior cervical ganglion or severance of the radix autonomica resulted in the loss of catecholamine staining in the pterygopalatine ganglion and the gland. Severance of the ophthalmic or infraorbital nerves had no effect on the VIPLI or the SPLI staining pattern in the gland.

Viral antibodies in normal tears.

Viruses are a common cause of eye infection. The local mucosal response, with production of antibodies released into tears, is believed to provide an important immune defense against these agents. However very little information exists on the viral specificity of normal tear immunoglobulins. In this study we obtained tears, parotid saliva and serum from 40 normal subjects without eye disease. Samples were examined by enzyme linked immunosorbent assay (ELISA) for antibodies to seven common viruses which invade mucosa: cytomegalovirus (CMV), Epstein Barr (EBV), herpes simplex type I (HSVI), measles, mumps, rubella and varicella zoster virus (VZV). The majority of normal tears contained antibodies to HSVI (73%) and EBV (65%), occasionally to mumps (30%), rubella (30%), and VZV (20%), and rarely to CMV (5%). Tear viral antibodies were mainly IgA class, but it was not unusual to find IgG antibodies to HSVI, VZV, rubella and measles. Tear and parotid saliva immunoglobulins from the same individual had entirely different viral reactivity. In most cases tear viral antibodies were reflected in serum viral antibodies, although the immunoglobulin class might differ. However, 15% of normal tears had antibodies to HSVI without detectable serum antibodies. From this study we conclude that normal tear immunoglobulins contain antibodies to common viruses, in particular to HSVI and EBV. These tear antibodies are mainly IgA, but can consist of IgG. Viral antibodies in tears are independent of the antibodies present in parotid saliva, suggesting that there is preferential homing of committed B lymphocytes to different mucosal surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Enkephalin-like immunoreactivity in neurons in the human pineal gland.

Adult human pineal glands were prepared for immunohistochemical analysis using antisera against Leu-enkephalin, neuropeptide Y, dopamine-beta-hydroxylase and vasoactive intestinal polypeptide. The material shows small neurons located in septae and along the capsule of the gland which exhibit enkephalin-like immunoreactivity. The neurons have fairly extensive dendritic arbors and immunoreactive axons are present in the septae and beneath the capsule, particularly in a perivascular location, and occasionally extend into lobules of the gland among parenchymal cells. No consistent immunoreactivity was observed with other antisera but bundles of axons exhibiting dopamine-beta-hydroxylase or neuropeptide Y-like immunoreactivity are observed in some of the material in a perivascular location.

Vasoactive intestinal polypeptide and the innervation of the human lacrimal gland.

Vasoactive intestinal polypeptide (VIP) is a biologically active neuropeptide found in both the peripheral and the central nervous systems. Previous studies have shown that VIP-like immunoreactive nerves are present in the uveal tissues of the human eye. The distribution of VIP-like immunoreactivity of the human lacrimal gland and sphenopalatine ganglion was studied. A lacy network of VIP-like immunoreactive nerve fibers was found in the lacrimal gland and was predominantly located along the basilar surface of the acinar epithelium and in the interstitial connective tissue of the gland. This pattern of innervation was nearly identical to the distribution of cholinesterase-positive fibers in human lacrimal glands. The VIP-like immunoreactive cell bodies were found throughout the sphenopalatine ganglion obtained at autopsy. The distribution of VIP-like immunoreactive nerves in the human lacrimal gland and sphenopalatine ganglion was generally similar to that described in mammalian and avian systems, although some differences were noted. Vasoactive intestinal polypeptide may represent an important cotransmitter or neuromodulator for the facial parasympathetic nerves that supply the eye and the lacrimal gland.

The effects of tobacco smoking on smooth pursuit eye movements.

It has recently been shown that tobacco smoking in normal human subjects induces a transient primary-position upbeat nystagmus. We studied the effects of tobacco smoking on smooth pursuit eye movements and found defects in both vertical and horizontal tracking during the first 5 minutes after smoking one cigarette. The smooth pursuit defect consisted of a reduction in upward tracking velocity and the superposition of saccadic square-wave jerks on both vertical and horizontal tracking eye movements. The degree of impairment in upward smooth pursuit correlated with the intensity of tobacco-induced nystagmus present when recording in darkness. We suggest that these alterations are due to summation of nystagmus on normal tracking eye movements rather than primary defects in the smooth pursuit system.

A pharmacological distinction between the long and short latency pathways of the human blink reflex revealed with tobacco.

In three, normal, human subjects, tobacco smoking was used as a pharmacological probe to modify differentially the direct and indirect pathways underlying the blink reflex. The latency of the indirect R2 component of the orbicularis oculis electromyogram evoked by electrical stimulation of the trigeminal supraorbital nerve transiently increased 20-80% after smoking, while the latency of the shorter latency, direct R1 component remained constant. The magnitude of both components of the blink reflex transiently decreased. The data demonstrate that tobacco smoking can differentially alter the long and short latency components of the blink reflex, and suggest that these effects result from modifications of central pathways sensitive to nicotine.

Superior oblique tenosynovitis (Brown's syndrome) as a manifestation of adult Still's disease.

A patient with adult Still's disease developed painful ophthalmoplegia due to inflammatory tenosynovitis of the superior oblique muscle and tendon sheath. Diagnosis was confirmed by computed tomographic scanning and resolution promptly obtained with corticosteroid therapy.

Oligoclonal IgG in tears.

We examined tears from patients with MS and systemic or eye diseases, and normal controls. Tears were isoelectrofocused on agarose gel, silver-stained, and immunofixated for IgG. In the cathodal portion of the gel (pH greater than or equal to 8.3), oligoclonal bands were detected in 14 of 21 (67%) MS tear samples. In most cases, these bands were not present in serum. Only 1 of 26 non-MS subjects showed two faint IgG tear bands, which were strongly present in serum. It appears that oligoclonal IgG bands can be detected in tears as well as in CSF of MS patients.

Multiple myeloma presenting with ocular inflammation.

We report an unusual case of intraocular myeloma that presented with signs and symptoms of endophthalmitis. The ocular findings in this case were the earliest indication of systemic myeloma associated with amyloidosis. Electrophoresis of the vitreous aspirate showed a monoclonal spike.