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Relative Afferent Pupillary Defect (RAPD) 1. Background Relative Afferent Pupillary Defect (RAPD) is a condition in which pupils respond differently to light stimuli shone in one eye at a time due to unilateral or asymmetrical disease of the retina or optic nerve. Swinging flashlight test or Marcus Gunn test is one of the most basic eye exams that neurologists, ophthalmologists, optometrists and primary care doctor perform when visiting most of their patients. The doctor asks her patient to look ahead then shines a penlight first toward one eye, then the other, alternating quickly to observe patient’s pupils’ response to the light. In case if both pupils do not show a similar response to the light stimuli, shone in one eye at a time, the patient will be diagnosed with RAPD or Marcus Gunn pupils. The results of this simple yet very important test help doctors in early diagnosis of many important eye related diseases such as optic neuropathy and multiple sclerosis. 2. Conditions Leading to a RAPD Optic nerve disorders: Unilateral optic neuropathies are common causes of an RAPD. If a condition is bilaterally symmetrical, there will not be an RAPD.  Optic neuritis: Even very mild optic neuritis with a minimal loss of vision can lead to a very strong RAPD.  Ischemic optic neuropathies: These include arteritic (Giant Cell Arteritis) and non-arteritic causes. Usually there will be a loss of vision or a horizontal cut in the visual field.  Glaucoma: While glaucoma normally is a bilateral disease, if one optic nerve has particularly severe damage, an RAPD can be seen.  Traumatic optic neuropathy: This includes direct ocular trauma, orbital trauma, and even more remote head injuries which can damage the optic nerve as it passes through the optic canal into the cranial vault.  Optic nerve tumor: This is a rare cause, and includes primary tumors of the optic nerve (glioma, meningioma) or tumors compressing the optic nerve (sphenoid wing meningioma, pituitary lesions, etc.)  Orbital disease: This could include compressive damage to the optic nerve from thyroid related orbitopathy (compression from enlarged extraocular muscles in the orbit), orbital tumors, or vascular malformations.  Radiation optic nerve damage  Miscellaneous optic neuropathies, such as Leber's optic neuropathy (usually eventually bilateral) and other inheritable optic neuropathies.  Optic nerve infections or inflammations: Cryptococcus can cause a severe optic nerve infection in the immunocompromised. Sarcoidosis can cause inflammation of the optic nerve. Lyme disease can affect the optic nerve.  Optic atrophy status: post papilledema - This is usually bilateral.  Surgical damage to the optic nerve: This could include damage following retrobulbar anesthesia; damage following orbital hemorrhage related to eye, orbital, sinus, or plastic surgery; damage following neurosurgical procedures such as pituitary tumor resection; and damage related to migration of an orbital plate after surgery to correct a blow-out fracture.

Retinal Causes of a Relative Afferent Pupillary Defect

Again, symmetrically bilateral retinal disease will not show an RAPD. Usually retinal disease has to be quite severe for an RAPD to be clinically evident.

 Ischemic retinal disease: Causes include ischemic central retinal vein occlusion, central retinal artery occlusion, severe ischemic branch retinal or arterial occlusions, severe ischemic diabetic or sickle-cell retinopathy.  Ischemic ocular disease (Ocular ischemic syndrome): This usually arises from obstruction of the ophthalmic or carotid artery on one side.  Retinal detachment: An RAPD can often be seen if the macula is detached, or if at least two quadrants of retina are detached.  Severe macular degeneration: If unilateral and severe, an RAPD can be seen. Usually the visual acuity would be less than 20/400.  Intraocular tumor: Retinal and choroidal tumors including melanoma, retinoblastoma, and metastatic lesion could lead to an RAPD if severe.  Retinal infection: Cytomegalovirus, herpes simplex, and other causes of retinitis can lead to an RAPD if there is extensive disease. Other Causes of a Relative Afferent Pupillary Defect  Amblyopia, if severe, can lead to a relative afferent pupillary defect. Usually the visual acuity would be 20/400, or worse.  Cerebral vascular disease: Usually, it is an optic nerve disorder that leads to an RAPD, rather than an optic tract or visual cortex disorder. However, there tends to be a higher percentage of crossed vs. uncrossed nerve fibers at the optic chiasm. Thus, in a patient with a homonymous hemianopia from an optic tract disorder, an RAPD could be seen in the eye with the temporal visual field defect. The nasal retina serves the temporal visual field, and these are the fibers that would cross at the chiasm (3).

3. RAPD Diagnosis and Challenges with the Swinging Flashlight Test Pupils are inspected for size, equality, and regularity during an eye exam. Each pupil should constrict quickly and equally during exposure to direct light and to light directed at the other pupil (the consensual light reflex). Using the swinging light test, physicians test and observe the pupillary response to consensual light in order to determine if there is a defect present. Normally, the pupil constriction does not change as the light is swung from eye to eye. When the light is moved quickly from eye to eye, both pupils should hold their degree of constriction. But even under the best condition, it is hard to perform this manual test accurately. Human factors, including examiner bias, light position variability, and endpoint determination, may all influence the identification and appropriate quantification of RAPD in patients [6]. Moreover, Other factors unique to any given individual such as dark irises, anisocoria or small pupils, and efferent defects may even make it much more difficult to detect small amounts of asymmetry in pupillary reactions (6). Although known to be an important physical sign, many well-practiced doctors report little incidence – not because the sign is not present, but because it is difficult or impossible to detect subtle abnormalities and it is rarely quantified (5). Misdiagnosis of optic nerve disease in primary stages, may lead to irreversible visual loss. In a recent study (7,8), the inter-examiner disagreement in the manual evaluation of pupillary reaction was as high as 39% (9). Such high amount of disagreement justifies the need for having more appropriate test methods.

4. Quantification of RAPD Various techniques have been described to quantify or measure APDs. These include the use of neutral density filters (10), cross-polarized filters (11), and subjective grading based on the amount of initial contraction and subsequent re-dilation of each pupil as the light is swung (12). Although these techniques have been shown to be effective and accurate, a number of factors influence the validity, variability, and reliability of such measurements. These techniques, although objective in their quantification, are unfortunately subjective in their endpoint.

5. Digital Marcus Gunn test as an alternative solution The development of personal computer-based infrared video instruments has allowed pupillography to enter the clinical arena. Measuring pupil diameter for refractive surgery, distinguishing Horner syndrome from physiologic anisocoria, quantifying the relative afferent pupillary defect, and plotting visual fields by means of graded pupil constriction to focal light stimuli are recent applications in ophthalmology. The primary objective of advanced and customized pupilometers is to eliminate the limitations in conventional testing procedures for measuring afferent eye defects. A special type of digital pupilometers perform the swinging flashlight test automatically based on the known guidelines and the standard procedure [13]. Several issues are being considered in designing a device for perfuming Marcus Gunn test accurately and consistently. Usually a mechanical frame is designed such that each eye is kept in full isolation from the other eye and external lighting sources. It means that no light can be sensed by the contralateral eye when a light source (which can be a full color LED) is emitting light to the right or the left eye. Image processing algorithms will be fed by real time images of the anterior segment of patients’ both eyes that taken by high resolution camera while one of the eyes is being stimulated with controllable lights automatically or manually. These computer algorithms separate pupils from other eye components and measure pupils size (Area, diameter, etc.) accurately. Usually these devices provide eye care professional with more information such as surface area of both pupils and dilation velocity which are not possible to measure with naked eye. This extra information is very useful not only for research purposes but also for improving diagnosing abilities of the doctor. Overall the quality of the test is improved by having better diagnostic accuracy, as well as documenting the test results for future follow-ups. References 1. AJ.Larner. A Dictionary of Neurological Signs. Second Edition. Springer 2006

                   © 2006, 2001 Springer Science+Business Media, Inc.

2. Relevant Afferent Pupillary Defect (RAPD) by Thomas J Walsh, MD on 3. Clinical Examination: Relative Afferent Pupillary Defect from Richmond Eye Associates 4. Pupil Anomalies :Reaction and Red Flags by Weon Jun, OD , FAAO; continuing education from CLLege of Optometry at Pacific University Oregon 5. sclerosis/c/19065/132247/marcus/#sthash.gKDyLRSJ.dpuf

6. Loewenfeld IE, Newsome DA. Iris mechanics. I. Influence of pupil size on dynamics of pupillary movements. Am J Ophthalmol 1971;71(1 Pt 2):347–62. 7. Du R, Meeker M, Bacchetti P, Larson MD, Holland MC, Manley GT: Evaluation of the portable infrared pupillometer. Neurosurgery, 57: 198-203, 2005. 8. Meeker M, Du R, Bacchetti P, Privitera CM, Larson MD, Holland MC, Manley GT: Pupil examination: validity and clinical utility of an automated pupillometer. J Neurosci Nurs, 37(1):34-40, 2005. 9. Wilson SF, Amling JK, Floyd SD, McNair ND: Determining interrater reliability of nurses' assessments of pupillary size and reaction. J Neurosci Nurs 20:189-192, 1988. 26. 10. Thompson HS, Corbett JJ, Cox TA. How to measure the relative afferent pupillary defect. Surv Ophthalmol 1981;26: 39–42. 11. Rosenberg ML, Oliva A. The use of crossed polarized filters in the measurement of the relative afferent pupillary defect. Am J Ophthalmol 1990;110:62–5. 12. Bell RA, Waggoner PM, Boyd WM, et al. Clinical grading of relative afferent pupillary defects. Arch Ophthalmol 1993; 111:938–42. 13. Volpe NJ, Plotkin ES, Maguire MG, et al. Portable pupillography of the swinging flashlight test to detect afferent papillary defects. Ophthalmology. 2000;107(10):1913-21

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