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.

<table><tbody><tr><td>Cotton-tipped applicators</td><td>Cardinal Health</td><td>5823043</td><td>Sterile plastic shaft applicators</td></tr><tr><td>Cotton-tipped applicators</td><td>AMD Ritmed</td><td>1191634</td><td>Autoclave-ready nonsterile applicators</td></tr><tr><td>Cotton-tipped applicators</td><td>Dukai Corporation</td><td>7166142</td><td>Sterile wood shaft cotton-tipped applicators</td></tr><tr><td>Kimwipes</td><td>Kimberly Clark Professional</td><td>1030492</td><td>Kimwipes tissue wipes</td></tr><tr><td>Unwaxed dental floss</td><td>Acclean</td><td>1552880</td><td>Spool of dental floss</td></tr><tr><td>Unwaxed dental floss</td><td>Sunstar</td><td>7127049</td><td>6 individual packages of floss</td></tr><tr><td>Unwaxed dental floss</td><td>Procter &amp;amp; Gamble</td><td>1090833</td><td>Single-use packets of floss</td></tr></tbody></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

Corneal Confocal Microscopy: A Novel Non-invasive Technique to Quantify Small Fibre Pathology in Peripheral Neuropathies

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. Conventional methods assess neurological deficits and electrophysiology and quantitative sensory testing quantifies functional alterations to detect neuropathy. However, the earliest damage appears to be to the small fibres and yet these tests primarily assess large fibre dysfunction and have a limited ability to demonstrate regeneration and repair. The only techniques which allow a direct examination of unmyelinated nerve fibre damage and repair are sural nerve biopsy with electron microscopy and skin-punch biopsy. However, both are invasive procedures and require lengthy laboratory procedures and considerable expertise. Corneal Confocal microscopy is a non-invasive clinical technique which provides in-vivo imaging of corneal nerve fibres. We have demonstrated early nerve damage, which precedes loss of intraepidermal nerve fibres in skin biopsies together with stratification of neuropathic severity and repair following pancreas transplantation in diabetic patients. We have also demonstrated nerve damage in idiopathic small fibre neuropathy and Fabry's disease.

Corneal Confocal microscopy is a non-invasive clinical technique which may be used to quantify C fibre damage to diagnose and stratify patients with increasing neuropathic severity.

The accurate quantification of peripheral neuropathy is important to define at risk patients, anticipate deterioration, and assess new therapies. ...

Ultrasound Cyclo Plasty in Eyes with Glaucoma

Glaucoma is a chronic disease caused by the progressive degeneration of the optical nerve fibers, resulting in decreased visual field that can lead to severe visual impairment, and eventually blindness. This manuscript describes a simple, surgeon-friendly, non-incisional technique, named Ultrasound Cyclo Plasty (UCP), for reducing intraocular pressure (IOP) in glaucoma patients. The technique determines a selective coagulation necrosis of the ciliary body; in addition, the stimulation of supra-choroidal and trans-scleral portions of the uveo-scleral outflow pathway has been recently proposed. UCP shows several technical improvements in ultrasound technology compared to previous techniques, providing more precise focusing on the target zone. The procedure is performed in the operating room under peribulbar anesthesia. Briefly, the coupling cone is put in contact with the eye and the ring probe, that contains six piezoelectric transducers which produce the ultrasound beams, is inserted inside it. Their proper centering over the ocular surface represents a crucial step for the correct targeting of the ciliary body. Sterile balanced salt solution is used to fill the empty spaces to ensure ultrasound acoustic propagation. Surgical treatment consists in the sequential automatic activation of each of the six transducers, for a total duration of less than 3 min. The patient leaves the hospital 1 h after the procedure with the treated eye patched. In the present study, 10 patients with open-angle glaucoma were followed-up during at least 12 months after the procedure. IOP was reduced at each interval compared to pre-operative, as well as the number of hypotensive medications. Twenty percent of patients did not respond to the treatment, and needed subsequent surgery to better control IOP. Treatment tolerability was good, with no cases of hypotony or phthisis. The UCP procedure is simpler, faster, safer, and less invasive than traditional cyclodestructive procedures with similar results in reducing IOP.

Glaucoma is a chronic disease with progressive degeneration of optic nerve fibers resulting in decreased visual field. Elevated intraocular pressure is considered the most important and the only treatable risk factor. This manuscript describes a simple, surgeon-friendly, non-incisional technique, named Ultrasound Cyclo Plasty, for reducing intraocular pressure in glaucoma patients.

Glaucoma is a chronic disease caused by the progressive degeneration of the optical nerve fibers, resulting in decreased visual field that can lead to ...

Behavior

Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients.
In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS.

Object From Motion (OFM) and Time-constrained stereo protocols are sensitive tools to identify monocular and binocular dynamic visual function deficits, which are uniquely affected in optic neuritis patients. Furthermore, these tests may be used as quantitative noninvasive tools to assess the extent of myelination along visual pathways.

In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to ...

Trabecular Meshwork Response to Pressure Elevation in the Living Human Eye

The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale behind this technique is the direct observation of the mechanical response of the TM to acute IOP elevation. Prior to scanning, IOP is measured at baseline and during IOP elevation. The limbus is scanned by spectral-domain optical coherence tomography at baseline and during IOP elevation (ophthalmodynamometer (ODM) applied at 30 g force). Scans are processed to enhance visualization of the aqueous humor outflow pathway using ImageJ. Vascular landmarks are used to identify corresponding locations in baseline and IOP elevation scan volumes. Schlemm canal (SC) cross-sectional area (SC-CSA) and SC length from anterior to posterior along its long axis are measured manually at 10 locations within a 1 mm segment of SC. Mean inner to outer wall distance (short axis length) is calculated as the area of SC divided by its long axis length. To examine the contribution of adjacent tissues to the effect IOP elevations, measurements are repeated without and with smooth muscle relaxation with instillation of tropicamide. TM migration into SC is resisted by TM stiffness, but is enhanced by the support of its attachment to adjacent smooth muscle within the ciliary body. This technique is the first to measure the living human TM response to pressure elevation in situ under physiological conditions within the human eye.

Trabecular meshwork (TM) migration into Schlemm&#8217;s canal space can be induced by acute pressure elevation by ophthalmodynamometer, and observed by spectral domain optical coherence tomography. The goal of this method is to quantify the morphometric response of the living outflow tract to acute pressure elevation in living tissues in situ.

The mechanical characteristics of the trabecular meshwork (TM) are linked to outflow resistance and intraocular pressure (IOP) regulation. The rationale ...

Evaluating Ocular Surface Squamous Neoplasia Using Anterior Segment HR-OCT

Anterior High-Resolution Optical Coherence Tomography in the Diagnosis and Therapeutic Monitoring of Ocular Surface Squamous Neoplasia

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. Traditionally, the diagnosis of OSSN relies on histopathological confirmation followed by a full-thickness biopsy. However, in the past two decades, the therapeutic approach to OSSN has shifted from surgical intervention to topical chemotherapy regimens in clinical settings. This shift emphasizes the need for less invasive or non-invasive methods to diagnose ocular surface pathologies. Among various imaging devices, commercially available high-resolution optical coherence tomography (HR-OCT) has emerged as a powerful tool for the characterization of OSSN. HR-OCT provides an in vivo, cross-sectional view of ocular surface lesions, offering an "optical biopsy" for OSSN with high sensitivity and specificity. It provides valuable information in differentiating intraepithelial or invasive OSSN from other benign lesions. Additionally, HR-OCT can be used to monitor the response to topical chemotherapy and to detect subclinical OSSN during follow-up visits. In this article, the scanning protocol for image acquisition is presented, and image interpretation for OSSN is outlined. This standardized, practical, and reproducible approach is recommended in clinical workflows and is expected to assist clinicians in the management of OSSN.

Author Spotlight: Anterior HR-OCT as a Non-Invasive Tool for Characterizing Ocular Surface Squamous Neoplasia

Anterior segment high-resolution optical coherence tomography (HR-OCT) is a promising non-invasive modality for the diagnosis and therapeutic evaluation of ocular surface squamous neoplasia (OSSN). Here, the system setup, scanning technique, and representative diagnostic results are presented.

Ocular surface squamous neoplasia (OSSN) is the most common tumor of the ocular surface, ranging from mild dysplasia to invasive squamous carcinoma. ...

Engineering

Three Different Protocols of Corneal Collagen Crosslinking in Keratoconus: Conventional, Accelerated and Iontophoresis

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been introduced as an efficient treatment option. In biological and chemical sciences, crosslinking refers to new chemical bonds formed between reactive molecules. Hence, the aim of corneal collagen CXL is to synthetically increase the formation of crosslinks between collagen fibrils in the corneal stroma. Despite the fact that the efficiency of the conventional CXL (C-CXL) protocol has already been shown in several clinical studies, it might benefit from improvements in duration of the procedure and removal of corneal epithelium. Hence, in order to provide a coherent evaluation of two new and optimized CXL protocols, we studied keratoconus patients who had undergone one of the three CXL treatments: iontophoresis (I-CXL), accelerated CXL (A-CXL), and conventional CXL (C-CXL). A-CXL is a 6 time faster CXL procedure using a ten time higher UVA irradiance but still including an epithelium removal. Iontophoresis is a transepithelial non-invasive technique in which a small electric current is applied to improve riboflavin penetration throughout the cornea. Using anterior segment optical coherence tomography (AS OCT) and in vivo confocal microscopy (IVCM), we conclude that regarding the depth of treatment penetration, conventional CXL protocol remains the standard for treating progressive keratoconus. Accelerated CXL seems to be a quick, effective and safe alternative to treat thin corneas. The use of iontophoresis is still being investigated and should be considered with greater caution.

Corneal collagen cross-linking (CXL) is the only conservative treatment currently available to halt keratoconus progression by improving the biomechanical rigidity of the corneal stroma. The aim of this manuscript is to highlight the methods of three different protocols of CXL: conventional CXL (C-CXL), accelerated CXL (A-CXL), and iontophoresis CXL (I-CXL).

Keratoconus is a bilateral and progressive corneal ectasia. In order to slow down its progression, corneal collagen cross-linking (CXL) has recently been ...

Assessing Early Stage Open-Angle Glaucoma in Patients by Isolated-Check Visual Evoked Potential

Recently, the isolated-check visual evoked potential (icVEP) technique was designed and has been reported to detect glaucomatous damage earlier and faster. It creates low spatial frequency/high temporal frequency bright stimuli and records cortical activity initiated primarily by afferents in the magnocellular ON pathway. This pathway contains neurons with larger volumes and axonal diameters, and it is preferentially damaged in early glaucoma, which can result in visual field loss. The study presented here uses standard operative procedures (SOP) of icVEP to obtain reliable results. It can detect visual function loss using a signal-to-noise ratio (SNR) corresponding to the defects of retinal nerve fiber layer (RNFL) in early stage open-angle glaucoma (OAG). A setting of 10 Hz and condition of 15% positive-contrast (bright) are selected to differentiate OAG patients and control subjects, with each check containing eight runs. Each run persists for 2 s (for 20 total cycles). A flowchart is constructed, which consists of pupil size and intraocular pressure over a 30 min rest period before each examination. Additionally, the testing order of eyes is performed to obtain reliable electroencephalographic signals. VEPs are recorded and analyzed automatically by software, and SNRs are derived based on a multivariate statistic. An SNR of &#8804; 1 is considered abnormal. A receiver-operating-characteristic (ROC) curve is applied to analyze the accuracy of group classification. Then, the SOP is applied in a cross-sectional study, showing that icVEP can detect glaucomatous visual function abnormality in the central visual field in the form of SNR. This value also correlates with the thickness thinning of RNFL and produces high classification accuracy for early stage OAG. Thus, it serves as a useful and objective diagnostic technology for the early detection of glaucoma.

The isolated-check visual evoked potential (icVEP) method is implemented here to assess the magnocellular ON pathway that is initially damaged in glaucoma. The study shows standard operative procedures using icVEP to obtain reliable results. It is proved to serve as a useful objective diagnosing technology for the early detection of glaucoma.

Recently, the isolated-check visual evoked potential (icVEP) technique was designed and has been reported to detect glaucomatous damage earlier and ...

Neuroscience

Biomechanical Characterization of Porcine Ocular Lens with Automated Compression

Automated Compression Testing of the Ocular Lens

The biomechanical properties of the ocular lens are essential to its function as a variable power optical element. These properties change dramatically with age in the human lens, resulting in a loss of near vision called presbyopia. However, the mechanisms of these changes remain unknown. Lens compression offers a relatively simple method for assessing the lens' biomechanical stiffness in a qualitative sense and, when coupled with appropriate analytical techniques, can help quantify biomechanical properties. A variety of lens compression tests have been performed to date, including both manual and automated, but these methods inconsistently apply key aspects of biomechanical testing such as preconditioning, loading rates, and time between measurements. This paper describes a fully automated lens compression test wherein a motorized stage is synchronized with a camera to capture the force, displacement, and shape of the lens throughout a preprogrammed loading protocol. A characteristic elastic modulus may then be calculated from these data. While demonstrated here using porcine lenses, the approach is appropriate for the compression of lenses of any species.

Author Spotlight: Advancing Understanding of Age-Related Lens Stiffness Changes 

We present an automated method for characterizing the effective elastic modulus of an ocular lens using a compression test.

The biomechanical properties of the ocular lens are essential to its function as a variable power optical element. These properties change dramatically ...

Bioengineering

Optic Nerve Sheath Point of Care Ultrasound: Image Acquisition

The goal of this protocol is to develop a standardized method for acquiring images of the optic nerve sheath and measuring the optic nerve sheath diameter (ONSD). Diagnostic ultrasound of the ONSD to detect intracranial hypertension has traditionally faced many problems because of methodologic discrepancies. Due to inconsistencies in the measuring techniques, the potential for ONSD to become a non-invasive bedside monitoring tool for ICP has been hampered. However, establishing a transparent, consistent methodology for measuring the ONSD would support its use as a valid and reliable method of identifying intracranial hypertension. This is important as it has both high sensitivity and specificity in acute care settings. This narrative review describes ONSD POCUS image acquisition, including patient positioning, transducer selection, probe placement, the acquisition sequence, and image optimization. Further, visual aids are provided to assist in real-time during image acquisition. This method should be considered for patients for whom there are concerns regarding intracranial hypertension but who do not have an intracranial monitor in place.

Point-of-care ultrasound (POCUS) of the optic nerve sheath diameter (ONSD) has been shown to be useful in identifying patients with increased intracranial pressure (ICP). However, the non-standardized technique for this POCUS has hampered its use. We present a standardized image acquisition protocol for use in the acute care setting.

The goal of this protocol is to develop a standardized method for acquiring images of the optic nerve sheath and measuring the optic nerve sheath diameter ...

Eye Exam

Source: Richard Glickman-Simon, MD, Assistant Professor, Department of Public Health and Community Medicine, Tufts University School of Medicine, MA
Proper evaluation of the eyes in a general practice setting involves vision testing, orbit inspection, and ophthalmoscopic examination. Before beginning the exam, it is crucial to be familiar with the anatomy and physiology of the eye. The upper eyelid should be slightly over the iris, but it shouldn&#39;t cover the pupil when open; the lower lid lies below the iris. The sclera normally appears white or slightly buff in color. The appearance of conjunctiva, a transparent membrane covering the anterior sclera and the inner eyelids, is a sensitive indicator of ocular disorders, such as infections and inflammation. The tear-producing lacrimal gland lies above and lateral to the eyeball. Tears spread down and across the eye to drain medially into two lacrimal puncta before passing into the lacrimal sac and nasolacrimal duct to the nose.
The iris divides the anterior from the posterior chamber. Muscles of the iris control the size of the pupil, and muscles of the ciliary body behind it control the focal length of the lens. The ciliary body also produces aqueous humor, which largely determines intraocular pressure (Figure 1). Cranial nerves II and III control pupillary reaction and lens accommodation; cranial nerve III controls upper lid elevation; cranial nerves III, IV, and VI control eye movement. The six cardinal directions of gaze are controlled by six extraocular muscles (Figure 2) innervated by cranial nerves III, IV, and VI.
Visual testing is an essential part of the ophthalmological exam and is also performed as a part of cranial nerve II assessment during the neurological exam. A focused image is projected onto the retina after its light passes through the cornea, pupil, lens, and vitreous body. The projection is upside down and reversed right to left, which means that light entering from the lower temporal field of vision strikes the upper nasal quadrant of the retina. Photosensitive cells of the retina respond by generating electrical impulses, which are relayed to the optic nerve and passed to the visual cortex through the optic tracts. The right and left visual cortices process images entering from the left and right visual fields, respectively.
<img alt="Figure 1" src="/files/ftp_upload/10149/10149fig1.jpg" /> 
Figure 1. Anatomy of the Eye. A diagram showing a sagittal view of the human eye with the structures labeled.
<img alt="Figure 2" src="/files/ftp_upload/10149/10149fig2.jpg" />
Figure 2. Muscles of the Eye. A cartoon showing a frontal view of the human eye and the extraocular muscles (labeled).

Anatomy and Physiology of Eye; Acuity and Vision Testing

Source: Richard Glickman-Simon, MD, Assistant Professor, Department of Public Health and Community Medicine, Tufts University School of Medicine, MA
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