Clinical Science W. Bruce Jackson, MD, FRCSC, editor
Spontaneous Eyeblink Activity Antonio A.V. Cruz, MD, Denny M. Garcia, BSc (Physics), Carolina T. Pinto, MD, and Sheila P. Cechetti, MD ABSTRACT Spontaneous blinking is essential for maintaining a healthy ocular surface and clarity of vision. The spontaneous blink rate (SBR) is believed to reflect a complex interaction between peripheral influences mediated by the eye surface and the central dopaminergic activity. The SBR is thus extremely variable and dependent on a variety of psychological and medical conditions. Many different methods have been employed to measure the SBR and the upper eyelid kinematics during a blink movement. Each has its own merits and drawbacks, and the choice of a specific method should be tailored to the specific needs of the investigation. Although the sequence of muscle events that leads to a blink has been fully described, knowledge about the neural control of spontaneous blinking activity is not complete. The tear film is dynamically modified between blinks, and abnormalities of the blink rate have an obvious influence on the ocular surface. KEY WORDS blinking, dopamine, ocular surface, spontaneous blinking activity, tear film, upper eyelid kinematics
I. Definition ye blinking, or simply blinking, is a fast eyelid movement that closes and opens the palpebral fissure. There are three types of blinks: spontaneous, reflex, and voluntary. While the latter depends only on the subject’s will, the former two are involuntary in nature and have dif-
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Accepted for publication November 2010. From the Department of Ophthalmology, Otorhinolaryngology, and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil. This work was supported by a grant from Brazilian Research Council (CNPq) #301865/2009-4. The authors have no commercial or proprietary interest in any concept or product discussed in this article. Single-copy reprint requests to Antonio A.V. Cruz, MD (address below). Corresponding author: Antonio Augusto Velasco Cruz, MD, Department of Ophthalmology, Otorhinolaryngology, and Head and Neck Surgery, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes, 3900, 14049-900 – Ribeirão Preto, SP – Brazil. Tel: +55 16 3602-2865. Fax: +55 16 3602-2860. E-mail:
[email protected]. ©2011 Ethis Communications, Inc. The Ocular Surface ISSN: 1542-0124. Cruz AAV, Garcia D, Pinto CT, Cechetti SP. Spontaneous eyeblink activity. 2011;9(1):29-41.
ferent functions. Reflex blinks occur only in response to a variety of different trigeminal, visual, and acoustic stimuli. Spontaneous blinking is an unconscious, transient, or brief closure of both upper eyelids that occurs in a highly symmetrical and coordinated fashion in the absence of any evident stimulus. This type of eyelid movement is essential for clarity of vision and for distributing the tear film over the ocular surface, thus maintaining tear film stability. Patients who cannot blink due to cicatricial or paralytic lagophthalmos develop severe eye exposure changes that may lead to loss of vision.
II. Measuring Blink Movement A. Methods It is not easy to measure a movement as fast as a spontaneous blink. Depending on its amplitude, a blink can be completed in less than 100 msec. Many different techniques have been employed to detect and register blinks. The evolution of these methods reflects advances in image and software technologies that have emerged in recent decades. In the past, the upper eyelid motion was registered with mechanical systems that are no longer employed. In those earlier systems, the eyelid was attached to a lever arm connected to a device that registered the lid motion.1 Examples include a writing pen,2 a potentiometer,3 a moving light-emitting diode (LED), and a photosensitive position detector.4 In contemporary research, more sophisticated methods are available. Each method has its own merits and limitations, and the appropriate choice is largely dependent on the nature and needs of the research that is being considered. Electrooculography (EOG) is a well-known method used to diagnose changes in the retinal pigment epithelium and also to record eye movements. In the early 1980s, the EOG began to be used for blinking analysis.5 Blinks are measured with the EOG when the electrodes are placed vertically above the eyebrow and on the malar prominence in line with the pupil.6 In this setting, an eyeblink is defined as a minimal voltage change during a certain period of time.7-9 Electromyography (EMG) is habitually used in blinking research to register the relationship between the orbicularis oculi muscle (OOM) and levator palpebral superioris muscle (LPS).10 To characterize OOM contraction, two miniature electrodes are taped to the lateral and medial portions of the upper eyelid near the lower margin.11 For
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Spontaneous Eyeblink Activity / Cruz, et al Outline I. Definition II. Measuring blink movement A. Methods B. Choosing the appropriate method III. Active and passive forces involved in the upper eyelid motion during a blink IV. Blink kinematics A. Amplitude and maximum velocity B. Main sequence: relationship between amplitude, maximum velocity, and duration V. Blink rate and interblink time intervals A. Distributions of interblink time intervals B. Development of blinking activity: age effects C. Effect of mental activity D. Neurological and psychiatric diseases E. Blink rate and ocular surface F. Blinking and tear dynamics G. Vision suppression during blinks VI. Eye movements associated with blinks VII. Upper eyelid abnormalities and blinking A. Facial nerve palsy B. Blepharospasm C. Graves’ upper eyelid retraction VIII. Summary
movements constitute a blink.17-19 Taking into consideration that blinks have a wide range of amplitudes, the method is not completely objective, and the observer has to decide which upper lid movements should be considered a blink. High-speed cameras provide a great deal of precision for movement detection.20 However, the amount of information that needs to be processed increases greatly with long observation times.21 This problem is overcome with the use of line image cameras22,23 or software that detects only a specific sign on the image.24-27 Another way to measure eyelid movements with video is to compute differences in brightness on images of the palpebral fissure during the closing and opening phases of the blink28 or to use videonystagmography.29 Infrared reflectance utilizes an infrared (IR) LED to illuminate the eye surface and another device, such as a phototransistor or a photodiode, that detects IR light reflected back from the eye.30 Both the LED and photodiode are mounted on an eyeglass frame. The blink signal is based on the difference between the light emitted and the light reflected from eyelid and eyeball31 and is processed by a microcomputer equipped with an analog-to-digital (AD) converter.32,33 The magnetic search coil method (MSC) was developed by Robinson34 to measure eye movements. This system offers high resolution, linearity, low drift, and low noise as compared to recording methods such as electrooculography or light reflection from parts of the eye.35 To record a blink, the subject is placed inside an oscillating magnetic field produced by a cubic frame. A small coil is taped to the upper eyelid close to the margin and above the pupil. Due to the flux generated by the magnetic field, a current is induced inside the coil. This sign is proportional to the sine of the angle between the coil and the magnetic field orientation35; because the eyelid rotates over the ocular surface, this measurement is relative to eyelid position. The spatial resolution achieved is about 0.25° or 0.05 mm. Although the MSC blink amplitude is always recorded in degrees, conversion from degrees to millimeters can be performed experimentally36 or by a trigonometric function.
LPS recording, a needle electrode is inserted through the preseptal skin,12 and the EMG is usually coupled to another system, such as a magnetic search coil or EOG that allows the registration of eyelid positional changes.13,14 The simultaneous use of EMG and EOG may be particularly useful for recording eyelid position OOM activity in situations where fixation of the head is not possible. In fact, it was demonstrated in freely moving children that such an approach replicated the temporal and amplitude characteristics of spontaneous and reflex blinks obtained with the magnetic search coil technique.15 Abbreviations Early attempts to record eyelid movements with images date back to AD Analog-to-digital 1951, when Gordon employed a movBSP Blepharospasm ing photographic paper that registered EMG Electromyography the light reflected on a small, polished EOG Electrooculography steel ball-bearing attached to the upIBI Interblink interval per eyelid.16 With the development IR Infrared of video and image processing techLED Light-emitting diode LPS Levator palpebral nologies, videotaping the eyelid fissure superior muscle became a popular method to register MRD Marginal reflex distance eyelid blinks. In its simplest form, a MSC Magnetic search coil commercial camera with a temporal OOM Orbicularis oculi muscle resolution of 30 frames per second PE Potential energy is employed to film the palpebral fisSBR Spontaneous blink rate sure during a certain period of time. SE Standard error The video is reviewed by one or two TFBUT Tear film breakup time observers, who then decide which lid 30
B. Choosing the Appropriate Method Depending on the aim of the study, some methods are more suitable than others. For example, a video system is the best method to register blinks in subjects who cannot be manipulated, such as infants. Or, if the investigator wants to study blink metrics in a laboratory, the MSC is the gold standard. Suppose the investigator wants to investigate whether a patient who is bilaterally anophthalmic displays a rhythmic orbicularis contraction, which might indicate that the spon-
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taneous blinking mechanism exists. In this case, MSC obviously is not feasible, and methods based on electrical signals are the only options.
III. Active and Passive Forces Involved in Upper Eyelid Motion During a Blink The upper eyelid movement in any type of blink is divided into two phases with different kinematic properties. The first is the down or closing phase characterized by a rapid lowering of the lid until the motion stops and the up or opening phase begins. Electromyographic studies have shown that the active forces that produce the movement of the upper eyelid during a blink are generated only by the OOM and LPS
Figure 1. Active and passive forces involved in the generation of upper eyelid motion during a spontaneous blink. The first two lines represent EMG records from the levator palpebrae superioris (LPS) and orbicularis oculi (OOM) muscles. The third line is a drawing that represents the changes in the potential energy (PE) stored by the stretched elastic components of the upper eyelid. The line at the bottom is the upper eyelid motion. When the upper eyelid is in its resting position, both the LPS and OOM have a balanced tonic activity. The sequence of events that leads to a blink initiates with LPS inhibition, followed by a burst of OOM contraction. Notice that LPS inhibition precedes and outlasts OOM contraction. In the down phase of the movement, the passive force represented by the third line is reduced to zero at the maximum amplitude (number 2). The potential energy starts to increase with the up-phase, which is dependent on LPS contraction. Numbers 1 and 3 indicate the points of maximum velocity of the down and up phases, respectively. (Adapted from Evinger et al13 and Esteban et al.88)
muscles.10,12,16,37,38 When the eyes are open, there is a balanced level of tonic activity in both muscles. The down phase of a blink is initiated with LPS inhibition, which precedes a burst of OOM contraction. LPS inhibition outlasts OOM contraction, which means that, for a short period of time near the end of the closing phase, both muscles are inactive. Once the downward lid movement stops, the OOM resumes its tonic activity and the LPS contracts, raising the lid. The up phase is thus entirely due to the active force generated by LPS contraction. In the closing phase, a passive force is produced by the release of the ligaments of the upper eyelid that is summed to the active force produced by OOM contraction. Figure 1 illustrates the sources of the active and passive forces involved in the upper eyelid motion during a blink. From a mathematical point of view, it has been shown that the whole movement is fit well with a model that considers the closing phase as a uniformly accelerated movement and the up phase as a harmonic oscillator.27
IV. Blink Kinematics A. Amplitude and Maximum Velocity Although it might seem natural to consider the amplitude of the down and up phases to be essentially identical, it is generally agreed that it is easier to determine the end point of amplitude of the down phase.27,39 The upper phase has an oscillatory nature, and it is not always easy to decide when the lid motion stops.39 In the context of this article, the expression blink amplitude refers to the down phase of the movement. In some clinical studies, the metrics of the upper eyelid motion during a set of blinks is not really measured, but is categorized with video records into different types of blinks. A small, almost undetectable movement of the upper eyelid has been termed a twitch blink. More noticeable movements are described as incomplete if the movement covers less than two thirds of the cornea and complete if the upper eyelid margin touches the lower eyelid, occluding the palpebral fissure.40,41 Another approach is to examine the lid excursion in sequential frames of an eyeblink videotape. With normal or high-speed cameras, the lid position is measured frame-by-frame in millimeters in order to quantify the final amplitude of the movement.21,28,42 As pointed out by Evinger, the upper lid margin movement during a blink is not represented by a vertical translation only.13 As the lid goes down, the margin rotates over the curved surface of the cornea. Thus, it seems natural to represent blink amplitude in degrees and not in millimeters.13,39 There are few data on the amplitude range and distribution of spontaneous blinks. Graphic analysis of data pooled from different subjects suggest that there is a continuum of blink amplitudes ranging from less than 10 degrees up to 60 degrees. The mean amplitude is considered to show a small but significant decrease in older patients, changing from 37.8 ± 4.6 SE degrees in 40-49-year-old normal subjects to 28.4 ± 2.5 SE degrees in 80-89-year-old normal subjects.43 However, this finding does not mean that there is any change in the central mechanisms that control
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Figure 2. Left: Distribution of blink amplitudes recorded in our laboratory from one subject during one hour of observation. Right: Amplitude values were converted to millimeters and divided by the distance between the upper eyelid margin and the pupil center. Values > 1.0 cover the pupil center.
blink amplitude, because the upper eyelid position is lower in the elderly. Figure 2 shows a typical amplitude distribution from 2463 blinks recorded with the magnetic search coil technique in a normal subject watching a video for 1 hour. When the amplitudes are converted to millimeters and divided by the distance of the upper eyelid margin to the pupil center (marginal reflex distance [MRD]), it is easy to see that only 4.5% of the blinks do not cover the pupil center. This proportion is variable, but in most normal individuals, the majority of blinks reach the pupil center.44 The maximum or peak velocity of the whole movement is always achieved during the down phase, reflecting the cessation of LPS muscle activity, the powerful force exerted by the OOM contraction superimposed on the passive force generated by the release of the suspensory ligaments of the upper eyelid. The up phase is slower and, as previously mentioned, results from LPS muscle contraction.13,36
B. Main Sequence: Relationship Between Amplitude, Maximum Velocity, and Duration The relationship between the amplitude and peak velocity is considered to be linear.11,13,43,44 This characteristic is known as main sequence, a term borrowed from astronomy. Originally, main sequence designates the relationship between the brightness of a star and its temperature. In studies of eye movement physiology, it designates the relationship between peak velocity and amplitude of eye saccades.45 By analogy, the concept was used in lid research to express the relationship between amplitude and velocity of lid movements. The main sequence slope (Figure 3) is considered to be indicative of aggregate motor neuron activity.46 The literature on the main sequence of spontaneous blinks is scant. Although some investigators have measured the main sequence slope in different situations,13,43,44,47-49 we are not aware of a systematic statistical analysis of the main sequence slope of spontaneous blinks. Some questions, eg, regarding the stability of the main sequence with repeated 32
measurements, the range of the interindividual differences, and the variance of the lid velocity in different amplitudes, have not been investigated. Depending on the magnitude of the slope of the main sequence of the closing phase, the duration of the down and up phases will moderately increase with amplitude.13,36
VI. Blink Rate and Interblink Time Intervals The number of blinks performed over a certain period of time constitutes the so-called spontaneous blink rate (SBR). To measure the SBR, a given subject is observed for a certain period of time and the total number of blinks performed is divided by the time of observation in minutes. The SBR is thus expressed as a mean rate in blinks/min. The determination of the “normal” SBR has attracted considerable attention from different areas of investigation. Since the paramount work of Ponder and Kennedy published in 1927,1 psychologists, neurologists, psychiatrists,
Figure 3. Main sequence. Amplitude and maximum velocity of spontaneous blinks registered in our laboratory in one subject who was watching a video.
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Figure 4. Two subjects observed in our laboratory with the same blink rate (16 b/min) and different interblink interval distributions. Top: Symmetrical. Bottom: Positively skewed.
optometrists, and ophthalmologists have published a large body of research on this topic. (For a comprehensive review up to 2001, see Doughty50). Although wide variability of the SBR is reported by different authors, it is agreed that the blinking activity depends on several factors, including age, ocular surface status, level of mental activity, and presence of specific neurologic and psychiatric diseases.
A. Distributions of Interblink Time Intervals Before discussing the main factors that influence the SBR, another concept should be taken into consideration when spontaneous blinking activity is studied. As shown by Ponder and Kennedy, the interval of time between consecutive blinks is not fixed.1 This means that subjects with the same SBR may blink in different ways. As shown in Figure 4, two subjects with identical SBR (16 b/min) may display different time intervals between blinks. The distribution of the interblink interval (IBI) of the first subject (top) is symmetrical and can be adjusted by a normal curve. On the other hand, the IBI of the second subject (bottom) is positively skewed and thus is better adjusted by a log normal curve. Ponder and Kennedy were probably the first to notice that the interblink intervals were quite variable between
subjects.1 They suggested that the shape of the IBI distributions was an individual characteristic and distinguished four patterns: J-shaped, irregular plateau, bimodal, and symmetrical. The J-shaped pattern corresponds to the positively skewed distribution displayed in Figure 4 (bottom figure). The main characteristic of this type of distribution is the occurrence of a large number of short IBI and a steadily decreasing number of longer IBI. According to Ponder and Kennedy, this pattern of IBI distribution was the most common, being found in 31 out of their 50 subjects. On the other hand, the symmetrical type (Figure 4, top figure) was the least frequent. This distribution results from a large number of IBI of average duration and an approximately equal number of shorter and longer IBI periods. Further investigation on this topic has led to some conflicting reports. For instance, Carney and Hill videotaped 20 normal subjects who were watching an educational movie during a period of 8.5 minutes and manually registered the time interval between blinks with the aid of an electronic timer. Although the authors suggested that the IBI distributions could be arbitrarily divided equally into three groups (small interblink period modal value, more or less symmetrical, and irregular), an inspection of their data showed that all distributions were positively skewed.41
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Figure 5. Scatterplot of data pooled from the literature on normal (quiet or fixating a stimulus) spontaneous blinking rate.17,43,53-56,58-61,82,100,130 The solid line does not represent a mathematical function. It just describes the tendency of SBR stabilization after adolescence.
Using a similar method, Zaman and Doughty registered the IBI distributions of 14 normal subjects during 5 minutes of fixation on a target.19 Nine subjects showed positively skewed IBI distributions (J type), four showed symmetrical distributions, and one subject displayed an irregular type of distribution. The shape of IBI distributions was the focus of two other articles. Naase et al examined the effect of corneal anesthesia on blink rate and confirmed that, under corneal anesthesia, the blink rate was reduced, but the IBI pattern did not change.51 The histogram of the whole group showed a typical positively skewed distribution. Doughty was the only investigator who proposed the symmetrical IBI distributions as the prototype of normal eyeblink activity. He speculated that regularly repeated blinks are more likely to distribute the tear film evenly on the eye surface.52 His opinion is not supported by the experimental data available in the literature. Most published IBI distributions are positively skewed, which means that they can be adjusted by LogNormal curves. Overall, we believe that there is a sampling problem in all studies designed to establish patterns of IBI distribution. Due to methodological problems (all investigations were undertaken with video analysis), the times of observation were quite short, usually in the range of 3-5 minutes. If one considers that a normal subject blinks more than 1,000 times per hour, it is clear that the sample formed by blinks that occur in 3-5 minutes is extremely small.
The first spontaneous eyelid movements are detected by ultrasonography in fetuses between 33 and 43 weeks of gestational age, with a rate of 0.10 blinks/min (6.2 movements per hour).58 During the neonatal period, Mantelli registered a mean SBR of 1.6 blinks/min in eight infants.59 Zametkin found a mean rate 0.714 blinks/min in a mixed group of neonates and infants up to 8 weeks of age.56 More recent studies reported higher rates (mean = 2.7 blinks/min) in infants up to 10-12 weeks of age.55 Interestingly, it has been demonstrated that even in infants, the SBR is modulated by environmental influences, such as the presentation of a new stimulus in the visual field.54,55 The SBR increases rapidly in children and adolescents and stabilizes in adults, with a mean value of 10 to 20 blinks/ min. The few studies that measured the SBR in elderly subjects did not find any change from the adult values.43,56,60,61
B. Development of Blinking Activity: Age Effects Very few studies have systematically investigated the development of spontaneous blinking activity. As expected, when quantitative data are registered at early ages, there is some variability in the literature. However, the data pooled in Figure 5 show that blink activity initiates during the fetal period and increases exponentially, reaching adult levels among teenagers.53-57
D. Neurological and Psychiatric Diseases SBR is widely recognized as a clinical marker of central dopaminergic activity. Although this concept has been recently challenged,79 it has been experimentally shown in monkeys that higher levels of dopamine are associated with high SBR.80,81 A positive correlation between SBR and the level of dopaminergic transmission is supported by a variety of
34
C. Effect of Mental Activity That the state of mind influences blink activity has been recognized since the beginning of the nineteenth century. There are a large number of studies that consistently show that SBR is sensitive to a variety of cognitive and emotional factors.5 Overall, SBR is increased during states of anxiety,62 visual fatigue,63,64 sleep deprivation,9,65-67 driving,68 or flying,69 and tasks that require speech60,70,71 or memory71or mental load.72-74 In contrast, SBR is reduced when the subject reads71,74 or views a text on video display.75-78
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clinical studies of diseases with dopamine dysfunction. For instance, low SBR is observed in conditions with hypodopamine activity, such as Parkinson disease,82-85 mental retardation and repetitive behavior disorder,86,87 progressive supranuclear palsy,88,89 alcohol abuse,1 recreational cocaine use,90 and attention deficit/hyperactivity disorder.91 SBR is high in conditions with hyperdominergic activity like Huntington disease,92 schizophrenia,8,93-95 or focal dystonia92 and in neurodevelopmental conditions, such as autism,87 Prader-Willi syndrome,96 depression,95 psychosis,97,98 panic disorder,62 and fragile X syndrome.99 Table 1 summarizes the reported quantitative data on the effect of different psychological and medical conditions on the blink rate.
E. Blink Rate and the Ocular Surface Earlier investigations on SBR were dominated by a conceptual framework that considered spontaneous blinking activity as an endogenous centrally regulated characteristic. This line of thinking led to a multitude of articles by psychologists, psychiatrists, and neurologists (see previous sections). With the advent of contact lenses and the growing interest in tear film analysis, it became clear that the ocular surface is of paramount importance in blink rate modulation. Conventional ophthalmological knowledge considered corneal sensation to be the main factor eliciting a blink. Classical experiments demonstrated that topical anesthesia reduces but does not abolish the SBR.51,100-102 The attempts to correlate tear film breakup time (TFBUT) with SBR have yielded some conflicting reports. Prause and Norn analyzed 32 healthy subjects and 29 patients suffering from primary Sjogren syndrome and found a moderate correlation for the controls (r = 0.33) and a stronger effect for the patients (r = 0.58).103 Collins et al used a video camera to measure the SBR in a group of nine young normal subjects and found a weak nonsignificant correlation (r = 0.38) between TFBUT and SBR.101 In contrast, more recent investigations conducted with large samples under controlled environmental conditions (humidity, light, and temperature) found significant negative correlations between TFBUT and SBR.104,105 Recent research has added interesting observations on the complex interactions between tear film, corneal sensation, and spontaneous blinks. Real-time digital movies of blink patterns and TFBUT showed that tear breakup is not a prerequisite for a blink.106 However, an elegant experiment using psychophysical data collected from a sample of normal subjects demonstrated a strong relationship between corneal sensation and tear film drying dynamics.107 Another line of evidence regarding the link between corneal surface and SBR comes from clinical studies of patients with dry eye. It has been consistently shown that the SBR of dry eye patients is higher than that of the normal population.28,77,100 The maximum time during which the subjects can keep their eyes open is also decreased among dry eye patients.100 The relationship between blinking and ocular surface is
Table 1. Quantitative effect of different conditions on the spontaneous blink rate SBR Effect
Conditions
Magnitude of SBR change (%) 35-274
Schizophrenia8
↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑
Reading or viewing a text on video display60,76
↓
53-55
Parkinson disease82,84
↓
37-40
Mental retardation and repetitive behavior disorder86
↓
30
Progressive supranuclear palsy89
↓
74
Alcohol abuse1
↓ ↓
75
Attention deficit/ hyperactivity disorder91
↓
25
Topical anesthesia51,75,100,102
↓ ↓
22-48
Speech60,70,71 Sleep
deprivation9,65-67
Anxiety62 Huntington
disease92
Depression95 Psychosis97 Dry eye28,100
Recreational cocaine
Graves’ orbitopathy44
use90
35-45 25 50 70 60 70-167 74
46
35
not restricted to wetting and protecting the cornea. Several recent studies have shown that shortly after a blink, the optical quality of the eye starts to degrade as a function of time. Sequential measurements of higher order aberrations,108-110 modulation transfer functions,111 retinal vessel contrast, contrast sensitivity,112,113 and corneal topography114,115 concur well, demonstrating that optimal optical performance starts to decrease 4-5 seconds after a blink. As expected, this effect is enhanced in patients with dry eye syndrome108,116 and has implications for contact lens users.113 The interaction between spontaneous blinking and the use of contact lenses has attracted considerable attention since the first lenses appeared on the market. In the early literature, several authors emphasized the importance of blink rate for the optimal position and movement of the lens, for cleaning its anterior surface, and, most important, for the fluid flow beneath the lens.117 In this context, the assessment of blink rate and its variation with different tasks became a critical issue in contact lens adaptation,118-123 and a blink beeper was even designed to remind patients to blink at regular intervals.124 An interesting question regards the relationship between contact lens use, blink, and quality of vision. It is a common finding that contact lens users experience intermittent blur-
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ring of vision. It has been shown that vision with contact lenses for a brief period of time after a blink is worse than vision with spectacles.125-127 Tear film changes and lens movement interact to explain the loss of sensitivity that accompanies blink movements in contact lens wearers.113
F. Blinking and Tear Dynamics The fact that OOM contraction during blinking is a key factor for both tear spreading over the ocular surface and lacrimal drainage has been a well-established concept since the nineteenth century, when clinicians noted that patients with facial palsy essentially had no lacrimal drainage.20 The active lacrimal pump process is mediated by a gradient of pressure changes in the lacrimal canaliculi and sac induced by orbicularis contraction and relaxation.128-132 Because the tears are drawn into the canaliculi during the up phase of the blinks,133 the blink rate is important for normal drainage.134 New technologies have shown that the tear film is dynamically regulated by blinking activity in order to maintain the integrity of the ocular surface. Spontaneous blinks modulate a continuum cycle of evaporation, spreading, and tear drainage.135-140 In the past, only the total tear volume changes in the palpebral fissure could be quantified by scintigraphy and by dye methods.141-145 With the advent of modern imaging technology, other methods, such as video meniscometry,146 interferometry,147,148 and real time optical coherence tomography, have been used to quantify the effect of blinking on tear dynamics.135,149-152 These sensitive techniques have shown that during normal blinking, there is a dynamic fluctuation of thickening and thinning of the tear film. The thinning rate that occurs during open-eye periods was estimated to be 4.0 µm/min. Evaporation is considered to be a major factor in this process.138-140 The dimensions of the upper tear meniscus are lower than those of the lower meniscus, and neither shows a significant variation immediately after a blink.135 However, the lower and upper menisci increase during the open eye interblink period.153 G. Vision Suppression During Blinks The existence of a spontaneous blinking activity implies that the visual input to the brain is momentarily disrupted several times per minute. In fact, it seems natural that every time the upper eyelid margins occlude the pupil, there is a transient decrement in retinal luminance. These blackout periods are not perceived, which means that the visual experience remains constant when the pupil is briefly occluded by the upper eyelid margin. However, when the luminance of the visual field is manipulated with similar amplitude and duration of a blink blackout, the changes are readily noticed.154 Thirty years ago, it was demonstrated for the first time that during voluntary blinking, the neuronal activity involved in visual perception is actively reduced. Maintaining the retinal illumination constant with light delivered to the retina through palatal transmission, it was possible to show that visual sensitivity is actively reduced during blinks.154 This phenomenon, known as blink suppression, 36
was confirmed in a series of subsequent investigations.155-160 Similar to the suppression associated with saccadic eye movements, blink suppression primarily affects the magnocellular system, the visual pathway tuned to low spatial and high temporal frequencies.156,161 Neuroimaging studies have demonstrated that blinks suppress activity at different locations of the visual cortex and in areas associated with awareness of environmental changes, such as the parietal and prefrontal cortex.155,162-165 Blinks also affect the performance of visual attention. Reaction time to visual stimuli is significantly increased when it occurs within 75 msec before the onset of a stimulus, and it is possible that the variance normally occurring in experiments that measure reaction times in vigilance tests is related to the blink-induced suppression.162
VI. Eye Movements Associated With Blinks For a long time, ophthalmologists have believed that during spontaneous blinking, the eye rotates upward. This notion originated from the classic article published by Sir Charles Bell in 1823 about the motion of the eye in facial palsy.166 The phenomenon described by Bell was confirmed many times when lid closure was restrained.167,168 However, careful laboratory investigations failed to demonstrate this phenomenon during spontaneous blinks. Several observations with the use of high-speed video analysis and a magnetic search coil have conclusively shown that the eye movement that accompanies any type of blink is a minute globe retraction associated with an inward, downward, and excyclo rotation.20,167,169-171 The eye movement is extremely fast and dependent on the original position of gaze. If, before blinking, the eye is in upgaze, the downward rotation increases. Similarly, abduction increases the inward rotation. At 10-20° downward and adduction the globe movement is minimal.170 The putative mechanism for the eye movements observed during blinks is a co-contraction of the vertical recti.170 VII. Upper Eyelid Abnormalities and Blinking A. Facial Nerve Palsy The loss of facial nerve function is a devastating event. In addition to the relaxation of the entire face, the palpebral fissure widens and the loss of orbicularis function leads to epiphora and paralytic lagophthalmos, posing a risk to vision. There are a myriad of etiologies that can be grouped into four categories: infectious, neoplastic, traumatic, and idiopathic.172 The last form is the most common and is synonymous with Bell’s palsy. The degree of OOM impairment is variable, and, in severe cases, the blink activity is completely abolished. In modern practice, reanimation of the upper eyelid is usually attempted with lid weighting. The desired amount of 99.99% (24 karats) gold is surgically implanted in the pretarsal area of the upper eyelid. The surgery is based on the increment of the downward passive force that is generated
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when the LPS relaxes. A quantitative evaluation of the efficacy of gold weight implants with a magnetic search coil was studied in six patients with unilateral facial nerve palsy.173 Preoperatively, the amplitude of the paretic eyelids was on average 28.6 ± 5.7% of the amplitude of the contralateral normal eyelids. After surgery, the amplitude improved to 42.6 ± 7.5% of control.173 No improvement was seen in the peak velocity of blink down phase, confirming that the effect of surgery was essentially passive. Not all patients with Bell’s palsy have a complete loss of the orbicularis function, and different degrees of recovery are commonly observed. In these patients, blink dysfunction is characterized by abnormalities in the main sequence of the closing phase on the palsied side. The peak velocity that normally increases linearly with blink amplitude shows a saturation curve that falls off the main sequence.11 Adaptive signs of hyperactivity characterized by elevation of the main sequence slope are sometimes seen in both palsied and normal lids.11,48
Figure 6. Eyelid movements in two patients with blepharospasm examined at the School of Medicine of Ribeirão Preto. Top: Only a high eyeblink rate is evident. Bottom: Normal blink movements are seen admixed with atypical movements and spasms.
B. Blepharospasm The so-called “benign” essential blepharospasm (BSP) is an extremely debilitating condition characterized by involuntary bilateral closure of the eyelids.88,174 The disease is considered to be a specific form of a spectrum of focal dystonias, which includes cranial cervical dystonia (Meige syndrome), spasm in the lower face and neck (Brueghel syndrome), and segmental and generalized dystonias.175 Most affected patients are seen by ophthalmologists because they frequently have symptoms of photophobia and dry eye and a high rate of spontaneous blinking.174,176 However, although it has been suggested that dry eye could act as an error signal for the development of high trigeminal excitability,177 there is no conclusion about the role of lacrimal film abnormalities in the pathophysiology of blepharospasm.176 Increased blink rate is a prominent sign of the disease in its initial form. In contrast to controls, who show higher blink rates during conversation than under rest conditions, patients with BSP have higher rates at rest than during conversation.174 This finding means that conversation may act as a trigger to reduce excitability to lid closure. The eyelid movements in BSP are not restricted to an increased blink rate. Depending on the severity of the disease, normal blinks coexist with abnormal pre-spastic blinks and true spasms with contraction of all protractor muscles (OOM, corrugators and procerus [Figure 6]). C. Graves’ Upper Eyelid Retraction Upper eyelid retraction is one of the most common and prominent signs of Graves’ orbitopathy. Since the nineteenth century, clinicians have noticed that the function of the retracted eyelid was not normal. The name of Stellwag is associated with infrequent and incomplete blinking, and the
Pochin sign refers to reduced blinking amplitude.178,179 The literature on the effects of Graves’ upper eyelid retraction on blink metrics is sparse. A recent set of data registered in our laboratory suggested that the absolute values of the blink amplitudes were similar for controls and Graves’ patients.44 However, taking into consideration that the lid margin of the patients was in a high position, 77.7% of the blinks did not reach the pupil center, as opposed to a rate of only 20% in the controls. The main sequence slope of the down and up phase was reduced compared to the values obtained for the controls. We believe that this finding does not reflect any change in blink control center. On the contrary, we think that peripheral LPS abnormalities, such as fibrosis and/or muscle hyperaction, explain these abnormalities. Interestingly, although the lids were retracted, the blink rate of the patients was not increased, confirming the old observation of Stellwag.
VII. Summary Spontaneous blinking activity is an extremely complex function. The existence of a blink pacemaker under dopaminergic control is a simple explanation for the fact that we start to blink as a fetus, and in early infancy, our blink activity is already influenced by different states of mind. A variety of neurological and psychiatric disorders also affect the so-called normal blink rate. The state of the ocular surface modulates the blink rate, and ophthalmologists are primarily concerned with the role of blinking in wetting and distributing the lacrimal film over the ocular surface. Cicatricial or paralytic problems that impair palpebral fissure closure lead to rapid corneal deterioration and blindness. Our organism has developed a sophisticated mechanism to distribute the lacrimal film
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over the pupil without any interference with our perception of the world. Every time we blink, there is an active process that suppresses our vision, keeping the perception of the visual scene constant. The metrics of the upper eyelid motion during spontaneous blinks has been well characterized by different methods of measurement. Blink amplitude is variable and the maximum velocity of the upper eyelid is linearly correlated to the amplitude. The slope of this relationship, designated as the main sequence, is considered to be a mark of the motor neuronal activity of the OOM. Although there is a vast literature on spontaneous blinks, many gaps exist in our knowledge. The brain areas that control the spontaneous blinks have not been fully characterized. We do not know if the interblink intervals follow a specific temporal pattern. The relationship between eye and lid movements in children with congenital ptosis who have been submitted to supramaximal LPS resection has not been investigated. The relationship between lid saccades, blink metrics, and corneal disease in Graves’ upper eyelid retraction is a matter that deserves further investigation. In summary, as is usual in science, the more we know, the more work needs to be done.
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