Writing and editorial assistance was provided under the direction of the authors by MedThink SciCom and funded by Domp&#233; US, Inc.

This study was approved by the institutional review board of the University of Miami, and the methods adhered to the tenets of the Declaration of Helsinki. All patients signed an informed consent form before participation. The reagents and the equipment used in the study are listed in the Table of Materials.
1. Pre-procedural preparation
<ol>
	<li>Perform corneal sensitivity testing on patients who are suspected of having ocular surface disease with alterations in the corneal nerves (Table 1)11,31,40,41,42.</li>
	<li>Ensure that testing is conducted before administering any eye drops, particularly anesthetic eye drops, as anesthetic eye drops decrease corneal sensitivity43 for a period (that varies by the type of eye drop used).</li>
	<li>Ensure that contact lenses are removed prior to testing.</li>
</ol>
2. Testing procedure
NOTE: Figure 1 depicts the overview of the testing procedure.
<ol>
	<li>Ask the patient to sit in a comfortable position on a chair.</li>
	<li>Use a cotton wisp (from a sterile cotton swab); unwaxed, unflavored dental floss; or a finely tapered tip of tissue as a stimulus for qualitative assessment of corneal sensitivity11,33 (Figure 1, step 2). 
	NOTE: Keep the testing stimulus in each lane for easy access.</li>
	<li>Instruct the patient to fixate on a target, such as a point or letter of a test chart that is straight ahead44 (Figure 1, step 3).</li>
	<li>If the patient presents with one suspected affected eye, test the unaffected cornea first. 
	NOTE: If a bilateral condition is suspected, first test the less affected cornea.</li>
	<li>Ask the patient to report when they feel the stimulus touch their cornea (Figure 1, step 4).</li>
	<li>Approach the patient&#39;s lateral side to reduce false positive responses caused by the patient reacting to the stimulus prior to contact44,45.</li>
	<li>Gently bring the stimulus in contact with the center of the cornea and observe the blink reflex, being careful not to touch the eyelids or lashes prior to touching the cornea (Figure 1, step 5).</li>
	<li>Record the corneal sensitivity of each eye using a 0-3 scale (Figure 1, step 6):&#160;Absent (0), reduced (1), normal (2), or increased/hypersensitive (3) response to stimulus.</li>
	<li>To perform a thorough examination, test all quadrants of the cornea3,11 in clockwise order using a new stimulus (Figure 1, step 5). 
	NOTE: A single measurement from the center of the cornea is generally sufficient to assess corneal sensitivity. Some patients may not tolerate repeated testing and may request that the provider stop after the center of the cornea is evaluated. However, if atypical sensation is present elsewhere in the cornea, testing only central sensation may lead to an inaccurate diagnosis.</li>
	<li>To test the limbus, ask the patient to fixate on a target above the horizontal plane44.</li>
	<li>Repeat the corneal testing procedure in the contralateral eye using an unused cotton wisp, dental floss, or tissue.</li>
</ol>
3. Recording the corneal sensitivity
<ol>
	<li>When the patient does not react to the stimulus and endorses not feeling the stimulus, put the score as &#34;Absent (0)&#34;.</li>
	<li>When the patient reports a minor sensation in their eye, which may or may not cause them to blink, assign the score as &#34;Reduced (1)&#34;. If using a cotton swab or tissue paper, apply slightly more pressure to touch a greater diameter of the cornea before the patient responds.</li>
	<li>When the patient blinks when the stimulus touches the cornea or exhibits a mild reflex (e.g., gently pulls away) and indicates that they felt the stimulus, assign the score as &#34;Normal (2)&#34;.</li>
	<li>When the patient exhibits a hypersensitive response, reports extreme discomfort or pain, strongly pulls away from the stimulus, or even jumps out of their chair, assign the score as &#34;Increased/hypersensitive (3)&#34;. 
	NOTE: Upon subsequent analysis, if the patient is found to have an unaffected eye, the response of the unaffected eye should then be used as a comparator when testing the affected eye.</li>
</ol>
4. Post-procedural steps
<ol>
	<li>Dispose of the cotton wisp, dental floss, or tissue on completion of the test.</li>
	<li>Ensure there are no infections or discomfort in the eyes.</li>
	<li>Return for follow-up examinations as per the ophthalmologist&#39;s instructions.</li>
</ol>

Assessing the Health of the Corneal Nerves in Ocular Surface Diseases

AG&#160;is or has been a consultant for Alcon, Allergan, Domp&#233; farmaceutici S.p.A., EyeCool Technology, Novaliq GmbH, Novartis, and Tarsus Pharmaceuticals. NL is or has been a consultant for Alcon, Allergan, Bausch &#38; Lomb, Bruder, Domp&#233; farmaceutici S.p.A., Ellex, EyePromise, Horizon, iCare, Innova Systems, LKC Pharma, Lumenis, NIDEK USA, Novartis, OCuSOFT, Orasis Pharmaceuticals, Reichert Technologies, RVL Pharmaceuticals, Sight Sciences, Sun Pharmaceuticals Industries Ltd, Tarsus Pharmaceuticals, Thea Pharma, Viatris, and Visionix USA.

This article described a procedure for performing corneal sensitivity testing using a qualitative method that is effective in assessing absent, reduced, normal, or increased corneal sensitivity. This procedure can be readily performed by eye care providers or physician extenders across clinical settings as it is cost-effective and accessible, requires minimal training and preparation, and can be performed quickly (approximately 30 s)8,33,37. The results are consistent across patients based on the authors&#39; experiences47, and the procedure can be easily incorporated into the eye care provider&#39;s workflow to support a clinical workup in patients with ocular diseases that affect the sensory corneal nerves.
As corneal sensitivity testing can be uncomfortable for the patient, it is important to test patients for whom corneal sensitivity testing would provide insight into the diagnosis of ocular surface diseases. We recommend performing corneal sensitivity testing in patients for whom there is a suspicion of ocular surface disease characterized by alterations in the corneal nerves, such as recalcitrant dry eye disease (including Sj&#246;gren&#39;s dry eye), ocular pain with neuropathic etiology, and neurotrophic keratitis. The suspicion of ocular surface disease is influenced by the patient&#39;s history and signs and symptoms8,31,48.
It is essential that corneal sensitivity testing be performed prior to administration of any eye drops, particularly anesthetic eye drops, to obtain accurate results11. Other factors to consider before assessing corneal sensitivity include that corneal sensitivity is greatest in the central cornea, that sensitivity decreases with older age, that the cornea is more sensitive in the periphery of elderly patients, and that corneal sensitivity is not affected by iris color49. Varying sensitivity with age could require baseline adjustment of normal sensitivity. An additional consideration during testing arises if the suspected disease is focally located (e.g., in the superior or inferior quadrant of the eye). In this case, the testing procedure should be modified to start in the affected eye in the area of suspected disease to minimize patient discomfort and to limit testing bias. Furthermore, patients may experience a transient loss in corneal sensitivity after some surgical procedures, such as cataract surgery or LASIK, and this should be considered when evaluating corneal sensitivity results30.
Corneal sensitivity scores inform the diagnosis of eye diseases characterized by alterations in the corneal nerves. For neurotrophic keratitis, reduced or absent corneal sensitivity is a key component of diagnosis11,31. Alterations in corneal sensitivity have been reported in dry eye disease and ocular neuropathic pain, among others3,8,12,24,25,26,27. However, corneal sensitivity alone is not sufficient to diagnose eye disease, and corneal sensitivity testing should be performed in conjunction with other tests to confirm the diagnosis. Notably, patients with a corneal sensitivity score within the normal range may receive a diagnosis of dry eye disease.
Limitations of the method include the qualitative nature of the assessment and the fact that corneal sensitivity testing indirectly infers the health of the corneal nerves. Alternative quantitative methods to assess corneal sensitivity are available; however, these methods have limitations, including high cost, challenges maintaining sterility, limited adoption into practice outside of a research setting, and increased time required to train personnel and conduct testing8,33,37. Quantitative methods are useful in a research setting for obtaining precise measurements of corneal sensitivity, but qualitative methods are more accessible and are generally sufficient in the clinic as part of a total clinical evaluation of a patient (e.g., medical history, clinical observations, etc.). Further studies are needed to assess the repeatability and reproducibility of qualitative corneal sensitivity testing methods and their level of agreement with quantitative methods.
In conclusion, this procedure for qualitative corneal sensitivity testing can be readily performed by eye care providers across clinical settings. Given its diagnostic value, corneal sensitivity testing should be included as part of the standard ocular surface examination for appropriate patients.

The main functions of the cornea are to protect the contents of the eye and to focus light on the retina1. The cornea is the most densely innervated structure in the human body, with 7000 nerve receptors per mm2, and, consequently, is one of its most sensitive tissues2,3. The corneal nerves originate from the ophthalmic branch of the trigeminal nerves and play a key role in maintaining corneal homeostasis and integrity by mediating protective reflexes such as blinking and tear production, providing trophic support to the ocular surface, and stimulating wound healing by releasing neuromediators1,4,5,6.
Damage with subsequent dysfunction of corneal nerves (hypersensitivity or hyposensitivity) can contribute to ocular surface diseases3,7,8. In fact, neurosensory abnormalities have been recognized as potential contributors to dry eye disease symptoms and signs and were incorporated into the 2017 Tear Film and Ocular Surface definition of dry eye disease: &#34;a multifactorial disease of the ocular surface characterized by a loss of homeostasis of the tear film, and accompanied by ocular symptoms, in which tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities play etiological roles6,9,10.&#34; Additionally, injury or dysfunction anywhere along the trigeminal nerve pathway can lead to neurotrophic keratitis (NK)11, a degenerative condition of the cornea; its stages include epithelial keratopathy, ulceration, and perforation, which may result in subsequent vision loss3.
Ocular surface pain can be categorized as nociceptive or neuropathic in origin8. In neuropathic ocular surface pain, nerves become hypersensitive because of the effects of a lesion or disease of the somatosensory pathway, which is often caused by maladaptive healing after trauma or surgery8. Abnormalities in corneal nerves have also been reported in other eye diseases, including glaucoma, thyroid eye disease, keratoconus, diabetic keratopathy, and Fuch&#39;s endothelial dystrophy12,13,14,15, and these findings are reproducible in animal models6,16,17. Notably, nerve abnormalities are not always identified as a component of eye disease, and a neurotrophic or neuropathic component to pain is often missed, underscoring the need for more diagnostic procedures to assess for the presence of nerve abnormalities18. Since ocular surface diseases may involve or induce corneal nerve dysfunction, a concise technique to assess corneal nerve function provides considerable diagnostic value.
Corneal sensitivity testing assesses a patient&#39;s reaction to brief corneal stimulation, providing functional insight into the status of the corneal nerves (absent, reduced, normal, or increased sensitivity)13,19. For example, in patients with neurotrophic keratitis, studies have found positive relationships between corneal sensitivity and parameters of corneal nerve innervation as assessed using in vivo confocal microscopy20,21, including corneal nerve fiber length (R2 = 0.2951, P = 0.0016)21. A positive correlation between corneal sensitivity and corneal nerve density has also been observed in herpes simplex keratitis (r = 0.55, P &#60; 0.001) and dry eye disease (r = 0.644; P = 0.045)22,23. However, abnormal corneal innervation does not always correlate with aberrant corneal sensitivity13.
Alterations in corneal sensitivity have been reported in dry eye disease (including both Sj&#246;gren&#39;s dry eye disease and diabetes mellitus-related dry eye disease); ocular neuropathic pain; neurotrophic keratitis; Fuch&#39;s endothelial dystrophy; and ocular treatments for glaucoma including topical drops, laser trabeculoplasty, slow coagulation transscleral cyclophotocoagulation, and micropulse ciliary body ablation3,8,12,24,25,26,27,28,29. Additionally, short-term hypoesthesia can be secondary to refractive surgery30. Reduced or absent corneal sensitivity is a hallmark of neurotrophic keratitis and is key to its diagnosis3,11,31. Reduced corneal sensitivity often presents with low tear production and epithelial disruption, and increased sensitivity can signal ocular neuropathic pain, although neuropathic mechanisms can contribute to pain even in individuals with reduced or normal corneal sensitivity9,32.
Corneal sensitivity can be assessed using either qualitative or quantitative methods, although quantitative methods are primarily limited to research settings2,8,11,31,33,34,35. Quantitative assessments are made using either the Cochet-Bonnet esthesiometer or Belmonte&#39;s gas esthesiometer; a new non-contact esthesiometer, the Corneal Esthesiometer Brill, was recently registered by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for corneal sensitivity testing36,37,38,39. The limitations associated with the Cochet-Bonnet and Belmonte&#39;s gas esthesiometers, including the cost and the challenge of maintaining sterility, render their use infrequent in clinical practice3. Qualitative methods can be easily performed by eye care providers or physician extenders, as they are low cost, readily available, and require little training and time8,33,37. Furthermore, there is insufficient published guidance on how to conduct corneal sensitivity testing and how corneal sensitivity scores as part of a clinical workup may inform diagnosis. Here, we detail a protocol for corneal sensitivity testing that is cost-effective, easy to comprehend, accessible, and can be readily adopted by eye care providers across clinical settings.

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			<td>Cardinal Health</td>
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			<td>Kimberly Clark Professional</td>
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			<td>Unwaxed dental floss</td>
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			<td>Sunstar</td>
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</table>

corneal sensitivity testing procedure for ophthalmologic and optometric patients

The cornea is the most densely innervated structure in the human body, making it one of the most sensitive tissues. Changes in corneal nerve sensitivity can be observed in several ocular surface diseases. Nerve sensitivity may be increased, as is often seen in patients with a neuropathic component to ocular pain, or decreased, as is seen in patients with neurotrophic keratitis. Corneal sensitivity testing involves assessing a patient's reaction to brief corneal stimulation, yields insight into the health of the corneal nerves, and provides diagnostic value for evaluating the health of the nerves and the interplay with the ocular surface. Currently, there is limited published guidance on how to conduct corneal sensitivity testing in a clinical setting. This article presents a protocol for testing corneal sensitivity using easy-to-use, low-cost materials that are readily accessible to eye care providers (either a cotton swab, a piece of dental floss, or a finely tapered tissue). This protocol allows for qualitative assessment of corneal sensitivity in which responses to corneal stimulation are rated from 0 (no response) to 3 (hypersensitive response). This test can be performed quickly (in approximately 30 s). Given its diagnostic value and accessibility, corneal sensitivity testing should be included as part of the standard eye examination for any patient undergoing an ocular surface examination.

This article aims to provide a detailed protocol for corneal sensitivity testing that is cost-effective, easy to comprehend, accessible, and can be readily adopted by eye care providers across clinical settings. The absence of corneal sensitivity results, or with no response from the patient, indicates that they did not feel the stimulus and is scored as 0. Reduced sensitivity manifests as a minimal observable response from the patient (although they may sometimes blink), in which they report barely feeling the stimulus and is scored as 1. Normal sensitivity is indicated by the patient acknowledging feeling the stimulus, blinking, and/or showing a mild reflex to pull away, and is scored as 2. Increased sensitivity manifests as a dramatic response to minor stimulation (e.g., the patient jumps up and/or indicates that the stimulus was painful or uncomfortable) and is scored as 3. Assessment of corneal sensitivity could lead to further assessments and potential diagnoses8,12,13,31.
Representative results of patient case reports of clinical presentation, relevant medical history, corneal sensitivity testing, and subsequent diagnoses are presented in Table 2; patients presented with medical histories and symptoms associated with ocular surface disease. Overall, two patients were diagnosed with neurotrophic keratitis after examination and corneal sensitivity testing. Of note, these two patients also had a history of diabetes mellitus or herpes simplex infection, which are key etiologies for neurotrophic keratitis46. Both patients presented with irritation and redness and received a score of 0 or 1 in the affected eye. Patients with a corneal sensitivity score of 2 (normal) were subsequently diagnosed with dry eye disease; patients with a corneal sensitivity score of 3 (hypersensitivity) were either diagnosed with dry eye disease or neuropathic corneal pain. Representative images of NK stages are presented in Figure 2.
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/66597/66597fig01.jpg" /> 
Figure 1: Overview of the corneal sensitivity testing procedure. <a href="https://www.jove.com/files/ftp_upload/66597/66597fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/66597/66597fig02.jpg" /> 
Figure 2: Stages of neurotrophic keratitis (NK). Representative images of&#160;fluorescein stain revealing superficial punctate keratopathy (stage 1 NK), persistent epithelial defect (stage 2 NK), and corneal ulcer (stage 3 NK) in individual patients with NK. <a href="https://www.jove.com/files/ftp_upload/66597/66597fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/66597/66597table1v2.jpg" /> 
Table 1: Factors supporting the decision to perform corneal sensitivity testing by ocular surface disease. Signs and symptoms supporting corneal sensitivity testing in patients with neurotrophic keratitis, neuropathic ocular pain, and dry eye disease. <a href="https://www.jove.com/files/ftp_upload/66597/66597_Table 1v2.xlsx" target="_blank">Please click here to download this Table.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/66597/66597table2v2.jpg" /> 
Table 2: Summary of outcomes using qualitative corneal sensitivity testing. Representative results of patient case reports of clinical presentation, relevant medical history, corneal sensitivity testing, and subsequent diagnoses. <a href="https://www.jove.com/files/ftp_upload/66597/66597_Table 2.xlsx" target="_blank">Please click here to download this Table.</a>

 Author Spotlight: Establishing a Practical and Cost-Effective Protocol for Corneal Sensitivity Testing in Clinical Settings

Corneal sensitivity testing provides insight into the health of the corneal nerves and helps diagnose ocular surface diseases. We present a concise protocol to qualitatively assess corneal sensitivity that can be readily used by eye care providers across clinical settings.

Corneal Sensitivity Testing Procedure for Ophthalmologic and Optometric Patients

The cornea is the most densely innervated structure in the human body, making it one of the most sensitive tissues. Changes in corneal nerve sensitivity ...

corneal-sensitivity-testing-procedure-for-ophthalmologic-optometric

Research

JoVE Journal

Medicine

1.5K Views.  Bascom Palmer Eye Institute. Corneal sensitivity testing provides insight into the health of the corneal nerves and helps diagnose ocular surface diseases. We present a concise protocol to qualitatively assess corneal sensitivity that can be readily used by eye care providers across clinical settings. 

Video:  Author Spotlight: Establishing a Practical and Cost-Effective Protocol for Corneal Sensitivity Testing in Clinical Settings

Manual Muscle Testing:  A Method of Measuring Extremity Muscle Strength Applied to Critically Ill Patients

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8 
This video demonstrates a protocol for MMT, which has been taught to &ge;43 research staff who have performed &gt;800 assessments on &gt;280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2.

Survivors of acute respiratory distress syndrome (ARDS) and critical illness frequently develop long-lasting muscle weakness. Manual muscle testing (MMT) is a standardized clinical examination commonly used to measure strength of peripheral skeletal muscle groups. This video demonstrates MMT using the 6-point Medical Research Council scale.

Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, ...

Corneal Donor Tissue Preparation for Endothelial Keratoplasty

Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes1,2. Since its inception, traditional full thickness corneal transplantation has been the treatment to restore sight in those limited by corneal disease. Some disadvantages to this approach include a high degree of post-operative astigmatism, lack of predictable refractive outcome, and disturbance to the ocular surface. The development of Descemet's stripping endothelial keratoplasty (DSEK), transplanting only the posterior corneal stroma, Descemet's membrane, and endothelium, has dramatically changed treatment of corneal endothelial disease. DSEK is performed through a smaller incision; this technique avoids 'open sky' surgery with its risk of hemorrhage or expulsion, decreases the incidence of postoperative wound dehiscence, reduces unpredictable refractive outcomes, and may decrease the rate of transplant rejection3-6.
Initially, cornea donor posterior lamellar dissection for DSEK was performed manually1 resulting in variable graft thickness and damage to the delicate corneal endothelial tissue during tissue processing. Automated lamellar dissection (Descemet's stripping automated endothelial keratoplasty, DSAEK) was developed to address these issues. Automated dissection utilizes the same technology as LASIK corneal flap creation with a mechanical microkeratome blade that helps to create uniform and thin tissue grafts for DSAEK surgery with minimal corneal endothelial cell loss in tissue processing.
Eye banks have been providing full thickness corneas for surgical transplantation for many years. In 2006, eye banks began to develop methodologies for supplying precut corneal tissue for endothelial keratoplasty. With the input of corneal surgeons, eye banks have developed thorough protocols to safely and effectively prepare posterior lamellar tissue for DSAEK surgery. This can be performed preoperatively at the eye bank. Research shows no significant difference in terms of the quality of the tissue7 or patient outcomes8,9 using eye bank precut tissue versus surgeon-prepared tissue for DSAEK surgery. For most corneal surgeons, the availability of precut DSAEK corneal tissue saves time and money10, and reduces the stress of performing the donor corneal dissection in the operating room. In part because of the ability of the eye banks to provide high quality posterior lamellar corneal in a timely manner, DSAEK has become the standard of care for surgical management of corneal endothelial disease.
The procedure that we are describing is the preparation of the posterior lamellar cornea at the eye bank for transplantation in DSAEK surgery (Figure 1).

Endothelial corneal transplantation is a surgical technique for treatment of posterior corneal diseases. Mechanical microkeratome dissection to prepare tissue results in thinner, more symmetric grafts with less endothelial cell loss and improved outcomes. Dissections can be performed at the eye bank prior to corneal transplantation surgery.

Over the past ten years, corneal transplantation surgical techniques have undergone revolutionary changes1,2. Since its inception, traditional full ...

Driving Simulation in the Clinic: Testing Visual Exploratory Behavior in Daily Life Activities in Patients with Visual Field Defects

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily life, despite similar visual deficits. We assume this could be due to variable development of compensatory strategies such as altered visual scanning behavior. Scanning compensatory therapy (SCT) is studied as part of the visual training after infarction next to vision restoration therapy. SCT consists of learning to make larger eye movements into the blind field enlarging the visual field of search, which has been proven to be the most useful strategy1, not only in natural search tasks but also in mastering daily life activities2. Nevertheless, in clinical routine it is difficult to identify individual levels and training effects of compensatory behavior, since it requires measurement of eye movements in a head unrestrained condition. Studies demonstrated that unrestrained head movements alter the visual exploratory behavior compared to a head-restrained laboratory condition3. Martin et al.4 and Hayhoe et al.5 showed that behavior demonstrated in a laboratory setting cannot be assigned easily to a natural condition. Hence, our goal was to develop a study set-up which uncovers different compensatory oculomotor strategies quickly in a realistic testing situation: Patients are tested in the clinical environment in a driving simulator. SILAB software (Wuerzburg Institute for Traffic Sciences GmbH (WIVW)) was used to program driving scenarios of varying complexity and recording the driver's performance. The software was combined with a head mounted infrared video pupil tracker, recording head- and eye-movements (EyeSeeCam, University of Munich Hospital, Clinical Neurosciences).
The positioning of the patient in the driving simulator and the positioning, adjustment and calibration of the camera is demonstrated. Typical performances of a patient with and without compensatory strategy and a healthy control are illustrated in this pilot study. Different oculomotor behaviors (frequency and amplitude of eye- and head-movements) are evaluated very quickly during the drive itself by dynamic overlay pictures indicating where the subjects gaze is located on the screen, and by analyzing the data. Compensatory gaze behavior in a patient leads to a driving performance comparable to a healthy control, while the performance of a patient without compensatory behavior is significantly worse. The data of eye- and head-movement-behavior as well as driving performance are discussed with respect to different oculomotor strategies and in a broader context with respect to possible training effects throughout the testing session and implications on rehabilitation potential.

Patients with visual deficits after stroke report about different constraints in daily life most likely due to variable compensatory strategies, which are difficult to differentiate in clinical routine. We present a clinical set-up which allows measurement of different compensatory head- and eye-movement-strategies and evaluating their effects on driving performance.

Patients suffering from homonymous hemianopia after infarction of the posterior cerebral artery (PCA) report different degrees of constraint in daily ...

Computerized Dynamic Posturography for Postural Control Assessment in Patients with Intermittent Claudication

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic conditions. As part of a diagnostic assessment, the early detection of postural deficits is important so that appropriate and targeted interventions can be prescribed. The Sensory Organization Test (SOT) on the EquiTest determines an individual&#39;s use of the sensory systems (somatosensory, visual, and vestibular) that are responsible for postural control. Somatosensory and visual input are altered by the calibrated sway-referenced support surface and visual surround, which move in the anterior-posterior direction in response to the individual&#39;s postural sway. This creates a conflicting sensory experience. The Motor Control Test (MCT) challenges postural control by creating unexpected postural disturbances in the form of backwards and forwards translations. The translations are graded in magnitude and the time to recover from the perturbation is computed.
Intermittent claudication, the most common symptom of peripheral arterial disease, is characterized by a cramping pain in the lower limbs and caused by muscle ischemia secondary to reduced blood flow to working muscles during physical exertion. Claudicants often display poor balance, making them susceptible to falls and activity avoidance. The Ankle Brachial Pressure Index (ABPI) is a noninvasive method for indicating the presence of peripheral arterial disease and intermittent claudication, a common symptom in the lower extremities. ABPI is measured as the highest systolic pressure from either the dorsalis pedis or posterior tibial artery divided by the highest brachial artery systolic pressure from either arm. This paper will focus on the use of computerized dynamic posturography in the assessment of balance in claudicants.

Individuals with intermittent claudication exhibit poor balance compared to healthy controls. Computerized dynamic posturography is an objective method for measuring an individual's postural responses to balance disturbances. This provides an objective reflection of the person&#x2019;s ability to respond to situations under which sensory stimuli are altered and unexpected perturbations occur.

Computerized dynamic posturography with the EquiTest is an objective technique for measuring postural strategies under challenging static and dynamic ...

Corneal Donor Tissue Preparation for Descemet's Membrane Endothelial Keratoplasty

Descemet&#8217;s Membrane Endothelial Keratoplasty (DMEK) is a form of corneal transplantation in which only a single cell layer, the corneal endothelium, along with its basement membrane (Descemet&#39;s membrane) is introduced onto the recipient&#39;s posterior stroma3. Unlike Descemet&#8217;s Stripping Automated Endothelial Keratoplasty (DSAEK), where additional donor stroma is introduced, no unnatural stroma-to-stroma interface is created. As a result, the natural anatomy of the cornea is preserved as much as possible allowing for improved recovery time and visual acuity4. Endothelial Keratoplasty (EK) is the procedure of choice for treatment of endothelial dysfunction. The advantages of EK include rapid recovery of vision, preservation of ocular integrity and minimal refractive change due to use of a small, peripheral incision1. DSAEK utilizes donor tissue prepared with partial thickness stroma and endothelium. The rapid success and utilization of this procedure can be attributed to availability of eye-bank prepared precut tissue. The benefits of eye-bank preparation of donor tissue include elimination of need for specialized equipment in the operating room and availability of back up donor tissue in case of tissue perforation during preparation. In addition, high volume preparation of donor tissue by eye-bank technicians may provide improved quality of donor tissue. DSAEK may have limited best corrected visual acuity due to creation of a stromal interface between the donor and recipient cornea. Elimination of this interface with transplantation of only donor Descemet&#39;s membrane and endothelium in DMEK may improve visual outcomes and reduce complications after EK5. Similar to DSAEK, long term success and acceptance of DMEK is dependent on ease of availability of precut, eye-bank prepared donor tissue. Here we present a stepwise approach to donor tissue preparation which may reduce some barriers eye-banks face in providing DMEK grafts.

Endothelial keratoplasty is a surgical technique continuously evolving as advancements result in transplantation of thinner grafts with each succession1. Here we present a technique for controlled manual tissue dissection to allow safe and repeatable separation of endothelium and Descemet&#39;s membranes from donor corneoscleral buttons for transplantation2.

Descemet&#8217;s Membrane Endothelial Keratoplasty (DMEK) is a form of corneal transplantation in which only a single cell layer, the corneal endothelium, ...

A Detailed Protocol for Physiological Parameters Acquisition and Analysis in Neurosurgical Critical Patients

Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ICP waveform, amplitude of pulse (AMP), the correlation of ICP amplitude and ICP mean (RAP), pressure reactivity index (PRx), ICP and arterial blood pressure (ABP) wave amplitude correlation (IAAC), and so on, can reflect intracranial status, predict prognosis, and can also be used as guidance of proper treatment. However, most of the clinicians focus only on the mean ICP value while ignoring these parameters because of the limitations of the current devices. We have recently developed a multimodality monitoring system to address these drawbacks. This portable, user-friendly system will use a data collecting and storing device to continuously acquire patients&#39; physiological parameters first, i.e., ABP, ICP, and oxygen saturation, and then analyze these physiological parameters. We hope that the multimodality monitoring system will be accepted as a key measure to monitor physiological parameters, to analyze the current clinical status, and to predict the prognosis of the neurosurgical critical patients.

Recently, we have developed a portable multimodality monitoring system for the monitoring of various physiological parameters in neurosurgical critical patients. Detailed protocols on how to use this multimodality monitoring system are presented here.

Intracranial pressure (ICP) monitoring is now widely used in neurosurgical critical patients. Besides mean ICP value, the ICP derived parameters such as ...

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

Corneal Epithelial Abrasion with Ocular Burr As a Model for Cornea Wound Healing

The murine cornea provides an excellent model to study wound healing. The cornea is the outermost layer of the eye, and thus is the first defense to injury. In fact, the most common type of eye injury found in clinic is a corneal abrasion. Here, we utilize an ocular burr to induce an abrasion resulting in removal of the corneal epithelium in vivo on anesthetized mice. This method allows for targeted and reproducible epithelial disruption, leaving other areas intact. In addition, we describe the visualization of the abraded epithelium with fluorescein staining and provide concrete advice on how to visualize the abraded cornea. Then, we follow the timeline of wound healing 0, 18, and 72 h after abrasion, until the wound is re-epithelialized. The epithelial abrasion model of corneal injury is ideal for studies on epithelial cell proliferation, migration and re-epithelialization of the corneal layers. However, this method is not optimal to study stromal activation during wound healing, because the ocular burr does not penetrate to the stromal cell layers. This method is also suitable for clinical applications, for example, pre-clinical test of drug effectiveness.

This protocol describes a method to inflict an abrasion to the ocular surface of the mouse, and to follow the wound healing process thereafter. The protocol takes advantage of an ocular burr to partially remove the surface epithelium of the eye in anaesthetized mice.

The murine cornea provides an excellent model to study wound healing. The cornea is the outermost layer of the eye, and thus is the first defense to ...

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies

The cornea has been used extensively as a model system to study wound healing. The ability to generate and utilize primary mammalian cells in two dimensional (2D) and three dimensional (3D) culture has generated a wealth of information not only about corneal biology but also about wound healing, myofibroblast biology, and scarring in general. The goal of the protocol is an assay system for quantifying myofibroblast development, which characterizes scarring. We demonstrate a corneal organ culture ex vivo model using pig eyes. In this anterior keratectomy wound, corneas still in the globe are wounded with a circular blade called a trephine. A plug of approximately 1/3 of the anterior cornea is removed including the epithelium, the basement membrane, and the anterior part of the stroma. After wounding, corneas are cut from the globe, mounted on a collagen/agar base, and cultured for two weeks in supplemented-serum free medium with stabilized vitamin C to augment cell proliferation and extracellular matrix secretion by resident fibroblasts. Activation of myofibroblasts in the anterior stroma is evident in the healed cornea. This model can be used to assay wound closure, the development of myofibroblasts and fibrotic markers, and for toxicology studies. In addition, the effects of small molecule inhibitors as well as lipid-mediated siRNA transfection for gene knockdown can be tested in this system.

A protocol for an ex vivo corneal organ culture model useful for wound healing studies is described. This model system can be used to assess the effects of agents to promote regenerative healing or drug toxicity in an organized 3D multicellular environment.

The cornea has been used extensively as a model system to study wound healing. The ability to generate and utilize primary mammalian cells in two ...

A Porcine Corneal Endothelial Organ Culture Model Using Split Corneal Buttons

Experimental research on corneal endothelial cells is associated with several difficulties. Human donor corneas are scarce and rarely available for experimental investigations as they are normally needed for transplantation. Endothelial cell cultures often do not translate well to in vivo situations. Due to the biostructural characteristics of non-human corneas, stromal swelling during cultivation induces substantial corneal endothelial cell loss, which makes it difficult to perform cultivation for an extended period of time. Deswelling agents such as dextran are used to counteract this response. However, they also cause significant endothelial cell loss. Therefore, an ex vivo organ culture model not requiring deswelling agents was established. Pig eyes from a local slaughterhouse were used to prepare split corneal buttons. After partial corneal trephination, the outer layers of the cornea (epithelium, bowman layer, parts of the stroma) were removed. This significantly reduces corneal endothelial cell loss induced by massive stromal swelling and Descemet&#39;s membrane folding throughout longer cultivation periods and improves general preservation of the endothelial cell layer. Subsequent complete corneal trephination was followed by the removal of the split corneal button from the remaining eye bulb and cultivation. Endothelial cell density was assessed at follow-up times of up to 15 days after preparation (i.e., days 1, 8, 15) using light microscopy. The preparation technique used allows a better preservation of the endothelial cell layer enabled by less stromal tissue swelling, which results in slow and linear decline rates in split corneal buttons comparable to human donor corneas. As this standardized organo-typically cultivated research model for the first time allows a stable cultivation for at least two weeks, it is a valuable alternative to human donor corneas for future investigations of various external factors with regards to their effects on the corneal endothelium.

Here, a step-by-step protocol for the preparation and cultivation of porcine split corneal buttons is presented. As this organo-typically cultivated organ culture model shows cell death rates within 15 days, comparable to human donor corneas, it represents the first model allowing long-term cultivation of non-human corneas without adding toxic dextran.

Experimental research on corneal endothelial cells is associated with several difficulties. Human donor corneas are scarce and rarely available for ...