The authors have no acknowledgements to declare.

All participants were provided both verbal and written informed consent before any study procedure. The protocol of the study was carried out in accordance with the Declaration of Helsinki and was approved by the local Institutional Review Board.
1. Automated Ocular Surface Workup
<ol>
	<li>Noninvasive break-up time (BUT) and lipid layer thickness (LLT) evaluation
	<ol>
		<li>&#34;Install the &#34;I.C.P.&#34; program by SBM Sistemi on the computer connected to the device.</li>
		<li>Apply the device on&#160;the slip lamp.</li>
		<li>Open the application and insert the patient&#8217;s data.</li>
		<li>Select the exam to be performed in the menu: select NIBUT to measure the noninvasive BUT or Interferometry to evaluate the lipid layer type and thickness grade.</li>
		<li>Instruct the patient to put the chin and forehead in the correct position on the slit lamp with the device, and place the camera of the device in front of patient&#8217;s eye at a correct distance (about 1-2 cm).</li>
		<li>Ask the patient to blink twice, and then stare without blinking for as long as possible.</li>
		<li>Keep the instrument still and click the proper button to acquire the video. The system will provide the value of noninvasive BUT (time in s) or LLT (grade from 1 to 7). 
		Note: These exams are completely noninvasive, and it is not necessary to use any topical anesthetic or vital staining for the acquisitions and measurements.</li>
		<li>Repeat the same procedure for the other eye, if required.</li>
	</ol>
	</li>
	<li>Meibomian gland loss (MGL) assessment
	<ol>
		<li>Install the &#8220;I.C.P.&#8221; program by SBM Sistemi on the computer connected to the device.</li>
		<li>Open the program&#160;and insert patient&#8217;s data.</li>
		<li>Select Meibomian gland in the menu of the exams.</li>
		<li>Apply the device on the slip lamp.</li>
		<li>Gently evert the lower eyelid using a cotton swab.</li>
		<li>Acquire an infrared image of the inner part of the lower eyelid in order to obtain a good quality image of the meibomian glands, which appear whitish.</li>
		<li>Draw the margins of the lower eyelid area&#160;on the touchscreen and click to fill the area. 
		Note: The system automatically calculates the percentage of meibomian gland area in relation the total area of the eyelid. In addition, it is possible to use ImageJ software (National Institute of Health; http://imagej.nih.gov/ij) to analyze the images, and measure the MGL value as the percentage of gland loss in relation to the total tarsal area of the eyelid, as previously described16.</li>
		<li>Repeat the same procedure for the other eye, if required.</li>
	</ol>
	</li>
	<li>Tear osmolarity measurement
	<ol>
		<li>Clip the single use test card with a microchip into the top of the pen. The pen confirms when the test card is correctly attached.</li>
		<li>Gently move down the lateral lower eyelid using a cotton swab to create a little space between the eyeball and the eyelid.</li>
		<li>Place the tip of the test card in this space to collect a sample of tear fluid (50 nL) from the inferior lateral meniscus of the tear film. The pen confirms when the tear fluid sample has been properly collected. 
		Note: It is recommended to collect tear fluid at the outermost area of the eyelid to minimize the risk of corneal injuries.</li>
		<li>Dock the pen in the reader unit. The system reader measures and displays on the screen the osmolarity of the tear in m&#937;/L.</li>
		<li>Repeat the same procedure for the other eye, if required. 
		Note: Separate test cards are needed for each eye.</li>
	</ol>
	</li>
	<li>Subjective symptoms assessment
	<ol>
		<li>Administer the Ocular Surface Disease Index (OSDI) questionnaire.</li>
		<li>Ask the patient the 12 questions of the OSDI questionnaire, and circle the number in the box that best represents each answer. 
		Note: The patient needs to answer 12 questions and give a score from 0 to 4 to each answer.</li>
		<li>Calculate the sum of the scores of each question, and the total number of questions answered.</li>
		<li>Assess the severity of patient&#8217;s ocular discomfort symptoms using the specific chart.</li>
	</ol>
	</li>
	<li>Fitzpatrick skin phototype assessment
	<ol>
		<li>Determine the patient&#8217;s Fitzpatrick skin phototype score basing on the color of the patient&#8217;s skin and its reaction to sun exposure, as previously described by Fitzpatrick17. 
		Note: Patient&#8217;s Fitzpatrick skin phototype score is necessary to determine the proper treatment parameters for each patient.</li>
	</ol>
	</li>
</ol>
2. Intense Pulsed Light (IPL) treatment
<ol>
	<li>Seat the patient comfortably in a treatment chair or lying down on a couch in office.</li>
	<li>Press the start button on the LCD touchscreen of the control unit to activate the device.</li>
	<li>Select the treatment for MGD by pressing the proper button on the LCD touchscreen.</li>
	<li>Select the desired treatment energy level using the up and down arrows on the LCD touchscreen and then press on the Tick button to confirm the choice. Six different energy levels can be chosen, ranging from 9 J/cm2 to 13 J/cm2. 
	Note: Treatment energy level is determined basing on the Fitzpatrick skin phototype grading scale from I to V (grade VI is not suitable for IPL treatment). Darker skins need lower energy levels.</li>
	<li>Validate each of the six safety features by pressing the six icon-buttons one by one and then press the Tick button to confirm that the procedure is performed in total safety. 
	Note: A summary with all the selections made will be displayed on the LCD touchscreen.</li>
	<li>Press the Tick button to start the device and wait a few seconds until the device is ready for the treatment.</li>
	<li>Put the eyewear or the eye mask on the patient&#8217;s eyes in order to protect eyes from the emitted therapeutic lights.</li>
	<li>Wear safety glasses to protect the eyes from the emitted light (200-1400 nm).</li>
	<li>Apply a thick layer of optical gel over the skin under the lower eyelid, from the edge of the nose up to the temple, in order to conduct the light and help to spread the energy homogeneously. 
	Note: The gel layer should be at least 1 cm thick.</li>
	<li>Take the device handpiece from the central unit and gently push its head in direct contact with the skin of the area to be treated.</li>
	<li>Press the Start button over the handpiece to emit a single treating IPL pulse.</li>
	<li>Apply 5 single IPL pulses distributed along the area, starting from the inner canthus and progressing to the temporal area, trying to be as close as possible to the lower eyelid margin in order to obtain the greatest effect. (Figure 1) 
	Note: The upper eyelids are not treated directly because of the risk of light penetration through the eyelid with possible light absorption and subsequent structural damage and inflammation of the intraocular pigmented structures (i.e., iris tissue, ciliary body, uveal tissues).</li>
	<li>Remove gently the optical gel from the treated skin area.</li>
	<li>Place a warm compress over the eyelids of both eyes for 2-3 min.</li>
	<li>Repeat the same procedure for the other eye, if required. 
	Note: The total time session lasts only few minutes (about 10 min). Based on the physician&#8217;s choice, the meibomian gland of the lower eyelid of both eyes could be manually expressed after IPL treatment using expressor forceps or two cotton swabs.</li>
</ol>
3. Post-treatment Therapy
<ol>
	<li>Prescribe topical steroid eye drops 2 times per day for the following 10 days after the first session of IPL. 
	Note: Patients are encouraged to continue warm compresses and topical lubricants use at least twice daily during the treatment period.</li>
	<li>Repeat IPL treatment after 15 and 45 days to complete the starting treatment protocol. 
	Note: The standard protocol consists of 3 sessions at day 0, day 15 and day 45. Another additional optional session could be performed at day 75, based on the physician and the patient&#8217;s preferences. Repeated treatments could be necessary at regular follow-up to maintain the efficacy after the 3 initial sessions (loading-phase), depending on the single clinical case.</li>
</ol>
4. Post-treatment Assessment
<ol>
	<li>Examine carefully the patient&#8217; eyes and eyelids at the slit lamp.</li>
	<li>Repeat noninvasive BUT, LLT, meibography and tear osmolarity to evaluate the treatment efficacy.</li>
	<li>Administer the OSDI questionnaire to the patient to evaluate the patient&#8217;s symptoms.</li>
	<li>Ask the patient whether he perceived improvements from his baseline ocular discomfort symptoms according to a 5-grade scale: none = 0, trace = 1, mild = 2, moderate = 3, high = 4. 
	Note: It is recommended to wait at least 15 days after the third session before evaluating the clinical results obtained with the procedure.</li>
</ol>

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P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=TFOS+DEWS+II+Definition+and+Classification+Report.">TFOS DEWS II Definition and Classification Report.</a> Ocul Surf. 15 (3), 276-283 (2017).</li><li>Buchholz, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Utility+assessment+to+measure+the+impact+of+dry+eye+disease.">Utility assessment to measure the impact of dry eye disease.</a> Ocul Surf. 4 (3), 155-161 (2006).</li><li>Uchino, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+eye+disease+and+work+productivity+loss+in+visual+display+users:+the+Osaka+study.">Dry eye disease and work productivity loss in visual display users: the Osaka study.</a> Am J Ophthalmol. 157 (2), 294-300 (2014).</li><li>Schaumberg, D. 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N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prospective+evaluation+of+intense+pulsed+light+and+meibomian+gland+expression+efficacy+on+relieving+signs+and+symptoms+of+dry+eye+disease+due+to+meibomian+gland+dysfunction.">Prospective evaluation of intense pulsed light and meibomian gland expression efficacy on relieving signs and symptoms of dry eye disease due to meibomian gland dysfunction.</a> Clin Ophthalmol. 11, 817-827 (2017).</li><li>Vegunta, S., Patel, D., Shen, J. 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The authors have nothing to disclose.

Intense pulsed light devices employ xenon gas-filled flash lamps to produce non-laser high intensity pulses of polychromatic non-coherent lights in a broad wavelength spectrum, from visible (515 nm) to infrared (1200 nm)18. The light energy pulse is released by the head of the handpiece by means of a sapphire or quartz block, and so directly applied onto the skin surface.
The mechanism of action of IPL systems is based on the principle of selective thermolisis, according to which certain targets, called chromophores, are capable of absorbing and then convert the light into heat energy12.
The particular characteristics of IPL devices make them capable of the simultaneous emission of different wavelengths lights (green, yellow, red and infrared), which allow to target at the same time the two main chromophores present in human skin, namely hemoglobin and melanin14,18.
Intense pulsed light treatment has been utilized for years in the field of dermatology, and recently, its use was translated to ophthalmology for the treatment of MGD, as a result of the improvement of dry eye symptoms in patients who underwent IPL treatment for facial rosacea19.
We describe the use and the therapeutic effects of a recently commercialized IPL device that was developed specifically for the treatment of MGD. In this device, IPL emission have been &#34;regulated&#34; in a multiple polychromatic train of calibrated and homogenously sequenced pulses.
To date, previous studies reported some improvements in terms of lid margin features (e.g., lid thickening and vascularity, telangiectasias, the number of plugged glands) and the secretion quality and expressibility of the meibomian glands after IPL treatment20,21,22,23,24. However, these measures are subjective, and prone to observer bias due to a low degree of standardization. Conversely, in order to overcome these drawbacks and improve the objectivity of the data, we used an automated quantitative analysis of ocular surface to evaluate the dry eye disease course after IPL treatment 25,26.
In our patients, noninvasive BUT significantly increased after IPL treatment, as previously reported by other research groups11,20,21,22,23,27, as a result of an improvement of tear film stability and a reduction in the tear evaporation rate. In addition, we found a significant increase of the tear film characteristics and the quality measured by LLT, in agreement with Craig, et al.27.
No significant changes were found for the tear osmolarity after IPL treatment, in agreement with other studies21,23,27. Although the recent TFOS DEWS II identified evaporation-induced tear hyperosmolarity as the core mechanism of dry eye disease8, MGD alone, without other ocular surface abnormalities, perhaps may not be sufficient to alter this parameter, particularly in milder or early stages of the disease. In fact, it should be highlighted that in our study, as well as in other MGD populations, tear osmolarity values were within the normal range21,26,28,29. Furthermore, the area of MGL did not change after IPL treatment in our patients. Conversely, the only previous study, which evaluated this parameter by noncontact infrared meibography, reported a 5% decrease of MGL after IPL treatment, suggesting a possible effect of this therapy upon meibomian gland parenchima30.
We investigated the patients&#39; subjective ocular discomfort by administering the OSDI questionnaire and a five-grade scale specifically focused on the patients&#39; perceived improvement in symptoms after the treatment. Despite the lack of a significant decrease of OSDI score after IPL, the vast majority of patients reported an overall improvement of ocular discomfort symptoms, and in about one third of the patients, this improvement was classified as moderate or high. These findings are in agreement with previous studies, which employed both validated questionnaires21,22,23,24,27,31 and specific scales of satisfaction11,20.
A careful patient selection is extremely important to obtain the best results from IPL. In fact, the treatment selectively acts on meibomian glands, whose dysfunction is the cause of evaporative DED, the most common subtype of dry eye. However, since DED is a multifactorial condition, the therapeutic approach should be dynamic, aiming at treating the dominating mechanism during the natural course of the disease. Therefore, IPL could be taken into consideration also in mixed forms of dry eye but in combination with other therapeutic options available.
IPL treatment provides an improvement of ocular surface parameters and discomfort symptoms. Regular repeated treatments may be required after the 3 starting sessions to maintain the beneficial effects of the procedure over the time. However, there is still no consensus about the time interval among treatments, which conversely should be customized according to the patient&#39;s satisfaction and changes of objective parameters.
The major limitation of the present study is represented by the lack of a control group. Additionally, the relatively small size of population might hamper the detection of further significance in case of small differences among parameters.
In conclusion, IPL for the treatment of patients with dry eye owing to meibomian gland dysfunction improved noninvasive break-up time and lipid layer thickness, as well as subjective symptoms.

Dry eye disease (DED) is an increasingly common condition and one of the most common reasons for clinical visits to an eye doctor1. The main symptom complained by patients affected by DED differs from various grades of redness and ocular discomfort to a chronic foreign body sensation, stinging, burning, itching, excessive tearing, pain, recurrent infections and transient visual disturbances2. The impact of DED on patients&#39; quality of life has been compared to that caused by moderate to severe angina or dialysis treatment3, and is associated with a restriction in daily activities and a loss of work productivity4.The recent definition of dry eye disease formulated by the TFOS DEWS II highlights its multifactorial nature, since different complex and heterogeneous alterations play a significant role in the onset and the maintenance of the disease2.
The vast majority of dry eye is caused by the so-called &#34;evaporative&#34; subtype that is mainly caused by meibomian gland dysfunction (MGD), a condition that affects up to 70% of the population in particular regions of the world5. Meibomian gland dysfunction is caused by a chronic alteration of the meibomian glands that are located inside the upper and lower eyelids. The disease is characterized by hyperkeratinization of the external duct of the glands and the obstruction of the orifices with insufficient, not functional, production of the external lipid layer of the tear film, resulting in tear instability6,7,8.
Currently, several different therapeutic strategies are available aiming at interrupting the vicious spiral of dry eye, and consist mainly of antibiotics, anti-inflammatory drugs, eyelid hygiene, warm compresses and tear substitutes9. However, these therapies are chronic and provide often only partial or short-term relief of symptoms, with subsequent compliance issues. Therefore, novel treatments with high efficacy and tolerability are desirable. In recent years, intense pulsed light (IPL) therapy has been widely used in dermatology for the treatment of different skin diseases such as acne, rosacea, telangiectasias and vascular and pigmented lesion (e.g., hemangiomas, venous malformations, port-wine stains)10. When the light is applied to the skin, it is absorbed by pigmented structures, such as blood cells and teleangectasias, with subsequent heat production that coagulates and destroys the abnormal blood vessels11. Recently, this technique was applied to the ophthalmic field for the treatment of DED owing to MGD. Several mechanisms have been postulated to explain the therapeutic effect of the procedure. Firstly, IPL treatment acts inducing thermal coagulation and selective ablation of superficial blood vessels and telangiectasias of the eyelids skin. Furthermore, the procedure reduces the release of inflammatory mediators and the levels of tear cytokines, which may promote the keratinization of mebomian glands terminal duct12,13. Secondly, the light energy transformed into heat causes the warming and liquefying of meibomian glands secretions, with subsequent melting and improved outflow11,14. More recently, other mechanisms such as the enhancement in collagen synthesis and connective tissue remodeling, the reduction in skin epithelial cell turnover, and the modulation of cellular inflammatory markers have also been hypothesized15.
In this study, we describe the use and the therapeutic effects of a recently commercialized IPL device, developed specifically for the treatment of MGD, in which IPL emission has been &#34;regulated&#34; in a multiple polychromatic train of calibrated and homogenously sequenced pulses. Therefore, the aim of this study is to describe the treatment procedure in detail, in order to spread it to the scientific medical community, giving the opportunity to ophthalmologists to expand their current armamentarium for the treatment of MGD.

<table border="0" cellpadding="0" cellspacing="0" width="1004">
	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:187px;">I.C.P. Tearscope</td>
			<td style="width:240px;">SBM Sistemi, Turin, Italy</td>
			<td style="width:103px;">1340864/R</td>
			<td style="width:475px;">Device for noninvasvive break-up time and lipid layer thickness evaluation</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:187px;">I.C.P. MGD</td>
			<td style="width:240px;">SBM Sistemi, Turin, Italy</td>
			<td style="width:103px;">15006</td>
			<td>Device performing infrared meibomography and meibomian gland loss evaluation</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:187px;">TearLab Osmolarity System</td>
			<td>TearLab Corporation, San Diego, CA, USA</td>
			<td style="width:103px;">83861QW</td>
			<td>Device for the measurement of tear osmolarity&#160;</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:187px;">E&#62;Eye</td>
			<td style="width:240px;">E-Swin, Paris, France</td>
			<td style="width:103px;"></td>
			<td>Intense pulsed regulated light treatment device</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:187px;">BM 900 Slit Lamp Biomioscropy</td>
			<td style="width:240px;">Haag-Streit, Koeniz, Switzerland</td>
			<td style="width:103px;">BM 900</td>
			<td>Slit Lamp Biomiscroscopy</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:187px;">Tobradex eye drops</td>
			<td style="width:240px;">Alcon Inc., Fort Worth, TX, USA</td>
			<td style="width:103px;">S01CA01</td>
			<td>Eye drops instilled immediately after the procedure in office</td>
		</tr>
	</tbody>
</table>

intense pulsed light for the treatment of dry eye owing to meibomian gland dysfunction

Dry eye disease (DED) is an increasingly common condition and one of the most common complaints of patients. The vast majority of DED is caused by the so-called &#34;evaporative&#34; subtype, that is mainly caused by meibomian gland dysfunction (MGD). Intense pulsed light (IPL) devices employ high intensity pulses of polychromatic lights with a broad range of wavelength (515-1200 nm). IPL treatment has been utilized for years in the field of dermatology, and then its use was applied to ophthalmology for the treatment of MGD. Recently, a new device employing IPL was specifically designed for the periocular application. This procedure determines the thermal selective coagulation and ablation of superficial blood vessels and telangiectasias of the eyelids skin, reducing the release of inflammatory mediators and tear cytokines levels, and improving meibomian glands outflow. IPL treatment is noninvasive and easy to perform, lasts for only a few minutes and can be conducted in an office setting. In the present study, 19 patients underwent 3 sessions of IPL treatment. After treatment, both mean noninvasive break-up time and lipid layer thickness grade significantly increased, as a result of an improvement of tear film stability and quality, respectively. Conversely, no statistically significant changes were found for meibomian gland loss and tear osmolarity. Furthermore, the vast majority of the treated patients (17/19; 89.5% of the total) perceived an improvement of their ocular discomfort symptoms after IPL treatment. Although IPL treatment provides an improvement of both ocular surface parameters and ocular discomfort symptoms after one cycle of three sessions, regular repeated treatments are usually required to maintain the persistence over the time of its beneficial effects.

Nineteen patients (7 males and 12 females, mean age 39.3 &#177; 7.0 years) (mean &#177; standard deviation) underwent IPL treatment between September 2016 and June 2017. Fifteen days after the third IPL treatment session, noninvasive BUT significantly increased from 7.6 &#177; 0.6 s to 9.8 &#177; 0.7 s (mean &#177; standard error of the mean) (p = 0.017), and LLT grade significantly improved from 2.3 &#177; 0.1 to 3.4 &#177; 0.3 (p = 0.003). No statistically significant changes were found for MGL and tear osmolarity (23.9 &#177; 3.6% vs 25.4 &#177; 2.6% and 304.5 &#177; 2.4 m&#937;/L vs 300.6 &#177; 2.4 m&#937;/L, respectively; always p&#62;0.05) (Figure 2). In addition, mean OSDI score did not differ significantly before and after the last treatment session (p&#62;0.05).
Seventeen patients (89.5% of the total) showed an improvement of ocular discomfort symptoms after the treatment (mean grade 2.0 &#177; 1.2 out of 4). Figure 3 shows the distribution of patients&#39; perceived improvement in symptoms according to the 5-grade scale. The perceived improvement in symptoms was significantly correlated with the improvement of LLT after the treatment (r = 0.476, p = 0.039).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/57811/57811fig1.jpg" /> 
Figure 1. Treatment area. The treatment area includes the lower eyelid, from the inner to the lateral canthus, the cheekbone and the temporal zone. Each red rectangle schematically represents the site of a single IPL pulse application. The numbers indicate the sequence of IPL pulse applications. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59828/59828fig1large.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/57811/57811fig2.jpg" /> 
Figure 2. Automated ocular surface workup before and after the treatment. Noninvasive BUT, lipid layer thickness (LLT), meibomian gland loss (MGL) and tear osmolarity before and 15 days after the third intense pulsed light treatment session. Error bars represent the standard error of the mean. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59828/59828fig2large.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/57811/57811fig3.jpg" /> 
Figure 3. Patients&#39; perceived improvement in dry eye symptoms after the treatment. The distribution of the patients according to the 5-grade scale about their perceived improvement in symptoms assessed 15 days after the third intense pulsed light treatment session. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/59828/59828fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Intense Pulsed Light for the Treatment of Dry Eye Owing to Meibomian Gland Dysfunction at JoVE.com

Intense Pulsed Light for the Treatment of Dry Eye Owing to Meibomian Gland Dysfunction

Dry eye disease is an increasingly common condition, which strongly impair patients&#39; life quality. Recently, a new device employing intense pulsed light, specifically designed for the periocular area, has been shown to improve tear film stability and ocular discomfort symptoms in dry eye disease owing to meibomian gland dysfunction.

Dry eye disease (DED) is an increasingly common condition and one of the most common complaints of patients. The vast majority of DED is caused by the ...

intense-pulsed-light-for-treatment-dry-eye-owing-to-meibomian-gland

Nanyang Technological University

Research

JoVE Journal

Medicine

14.8K Views.  Carones Ophthalmology Center. Dry eye disease is an increasingly common condition, which strongly impair patients' life quality. Recently, a new device employing intense pulsed light, specifically designed for the periocular area, has been shown to improve tear film stability and ocular discomfort symptoms in dry eye disease owing to meibomian gland dysfunction.

Video: Intense Pulsed Light for the Treatment of Dry Eye Owing to Meibomian Gland Dysfunction

The Measurement and Treatment of Suppression in Amblyopia

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current estimates put the prevalence of amblyopia at approximately 1-3%1-3, the majority of cases being monocular2. Amblyopia is most frequently caused by ocular misalignment (strabismus), blur induced by unequal refractive error (anisometropia), and in some cases by form deprivation.
Although amblyopia is initially caused by abnormal visual input in infancy, once established, the visual deficit often remains when normal visual input has been restored using surgery and/or refractive correction. This is because amblyopia is the result of abnormal visual cortex development rather than a problem with the amblyopic eye itself4,5 . Amblyopia is characterized by both monocular and binocular deficits6,7 which include impaired visual acuity and poor or absent stereopsis respectively. The visual dysfunction in amblyopia is often associated with a strong suppression of the inputs from the amblyopic eye under binocular viewing conditions8. Recent work has indicated that suppression may play a central role in both the monocular and binocular deficits associated with amblyopia9,10 .
Current clinical tests for suppression tend to verify the presence or absence of suppression rather than giving a quantitative measurement of the degree of suppression. Here we describe a technique for measuring amblyopic suppression with a compact, portable device11,12 . The device consists of a laptop computer connected to a pair of virtual reality goggles. The novelty of the technique lies in the way we present visual stimuli to measure suppression. Stimuli are shown to the amblyopic eye at high contrast while the contrast of the stimuli shown to the non-amblyopic eye are varied. Patients perform a simple signal/noise task that allows for a precise measurement of the strength of excitatory binocular interactions. The contrast offset at which neither eye has a performance advantage is a measure of the "balance point" and is a direct measure of suppression. This technique has been validated psychophysically both in control13,14 and patient6,9,11 populations.
In addition to measuring suppression this technique also forms the basis of a novel form of treatment to decrease suppression over time and improve binocular and often monocular function in adult patients with amblyopia12,15,16 . This new treatment approach can be deployed either on the goggle system described above or on a specially modified iPod touch device15.

Amblyopia is a developmental disorder of the visual cortex that is often accompanied by strong suppression of one eye. We present a new technique for measuring and treating interocular suppression in patients with amblyopia that can be deployed using virtual reality goggles or a portable iPod Touch device.

Amblyopia, a developmental disorder of the visual cortex, is one of the leading causes of visual dysfunction in the working age population. Current ...

The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient's quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient's response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. The Goeckerman regimen, formulated for the treatment of psoriasis, consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). The following protocol is for the administration of Goeckerman therapy for the treatment of moderate-to-severe psoriasis.

Psoriasis is a  chronic, immune-mediated inflammatory skin disease affecting approximately 2-3%  of the population. The Goeckerman regimen consists of ...

Network Analysis of Foramen Ovale Electrode Recordings in Drug-resistant Temporal Lobe Epilepsy Patients

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control seizures. However, a significant minority of patients continues to exhibit post-operative seizures, even in those cases in which the suspected source of seizures has been correctly localized and resected. The protocol presented here combines a clinical procedure routinely employed during the pre-operative evaluation of temporal lobe epilepsy (TLE) patients with a novel technique for network analysis. The method allows for the evaluation of the temporal evolution of mesial network parameters. The bilateral insertion of foramen ovale electrodes (FOE) into the ambient cistern simultaneously records electrocortical activity at several mesial areas in the temporal lobe. Furthermore, network methodology applied to the recorded time series tracks the temporal evolution of the mesial networks both interictally and during the seizures. In this way, the presented protocol offers a unique way to visualize and quantify measures that considers the relationships between several mesial areas instead of a single area.

This protocol describes a procedure to track the evolution of mesial network measures in temporal lobe epilepsy (TLE) patients. It is based on the combination of intracranial recordings with a novel numerical technique for data analysis. Specifically, we present a protocol for network analyses of foramen ovale recordings.

Approximately 30% of epilepsy patients are refractory to antiepileptic drugs. In these cases, surgery is the only alternative to eliminate/control ...

Using Retinal Imaging to Study Dementia

The retina offers a unique &#8220;window&#8221; to study pathophysiological processes of dementia in the brain, as it is an extension of the central nervous system (CNS) and shares prominent similarities with the brain in terms of embryological origin, anatomical features and physiological properties.&#160; The vascular and neuronal structure in the retina can now be visualized easily and non-invasively using retinal imaging techniques, including fundus photography and optical coherence tomography (OCT), and quantified semi-automatically using computer-assisted analysis programs. Studying the associations between vascular and neuronal changes in the retina and dementia could improve our understanding of dementia and, potentially, aid in diagnosis and risk assessment.&#160; This protocol aims to describe a method of quantifying and analyzing retinal vasculature and neuronal structure, which are potentially associated with dementia. This protocol also provides examples of retinal changes in subjects with dementia, and discusses technical issues and current limitations of retinal imaging.

The retina shares prominent similarities with the brain and thus represents a unique window to study vasculature and neuronal structure in the brain non-invasively. This protocol describes a method to study dementia using retinal imaging techniques. This method can potentially aid in diagnosis and risk assessment of dementia.

The retina offers a unique &#8220;window&#8221; to study pathophysiological processes of dementia in the brain, as it is an extension of the central ...

Isolation of Adipose Derived Regenerative Cells for the Treatment of Erectile Dysfunction Following Radical Prostatectomy

Stem cells are used in many research areas within regenerative medicine in part because these treatments can be curative rather than symptomatic. Stem cells can be obtained from different tissues and several methods for isolation have been described. The presented method for the isolation of adipose-derived regenerative cells (ADRCs) can be used within many therapeutic areas because the method is a general procedure and, therefore, not limited to erectile dysfunction (ED) therapy. ED is a common and serious side effect to radical prostatectomy (RP) since ED often is not well treated with conventional therapy. Using ADRC&#8217;s as treatment for ED has attracted great interest due to the initial positive results after a single injection of cells into the corpora cavernosum. The method used for the isolation of ADRC&#8217;s is a simple, automated process, that is reproducible and ensures a uniform product. Furthermore, the sterility of the isolated product is ensured because the entire process takes place in a closed system. It is important to minimize the risk of contamination and infection since the stem cells are used for injection in humans. The whole procedure can be done within 2.5-3.5 hours and does not require a classified laboratory which eliminates the need for shipping tissue to an off-site. However, the procedure has some limitations since the minimum amount of drained lipoaspirate for the isolation device to function is 100 g.

Precise disclosure of methods and protocols is crucial for large scale uptake of stem cell therapies. Here, we present a protocol to isolate adipose-derived regenerative cells, used for a single intracavernous injection as treatment of erectile dysfunction (ED) following radical prostatectomy (RP).

Stem cells are used in many research areas within regenerative medicine in part because these treatments can be curative rather than symptomatic. Stem ...

A Rabbit Model of Aqueous-Deficient Dry Eye Disease Induced by Concanavalin A Injection into the Lacrimal Glands: Application to Drug Efficacy Studies

Dry eye disease (DED), a multifactorial inflammatory disease of the ocular surface, affects 1 in 6 humans worldwide with staggering implications for quality of life and health care costs. The lack of informative animal models that recapitulate its key features impedes the search for new therapeutic agents for DED. Available DED animal models have limited reproducibility and efficacy. A model is presented here in which DED is induced by injecting the mitogen concanavalin A (Con A) into the orbital lacrimal glands of rabbits. Innovative aspects of this model are the use of ultrasound (US) guidance to ensure optimal and reproducible injection of Con A into the inferior lacrimal gland; injection of Con A into all orbital lacrimal glands that limits compensatory production of tears; and use of periodic repeat injections of Con A that prolong the state of DED at will. DED and its response to test agents are monitored with a panel of parameters that assess tear production, the stability of the tear film, and the status of the corneal and conjunctival mucosa. They include tear osmolarity, tear break-up time, Schirmer&#39;s tear test, rose bengal staining, and tear lactoferrin levels. The induction of DED and the monitoring of its parameters are described in detail. This model is simple, robust, reproducible, and informative. This animal model is suitable for the study of tear physiology and of the pathophysiology of DED as well as for the assessment of the efficacy and safety of candidate agents for the treatment of DED.

This article describes the development of a method to induce acute or chronic dry eye disease in rabbits by injecting concanavalin A to all portions of the orbital lacrimal gland system. This method, superior to those already reported, generates a reproducible, stable model of dry eye suitable for the study of pharmacological agents.

Dry eye disease (DED), a multifactorial inflammatory disease of the ocular surface, affects 1 in 6 humans worldwide with staggering implications for ...

Establishment of a Severe Dry Eye Model Using Complete Dacryoadenectomy in Rabbits

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic step. Despite advances in our understanding of DED, significant knowledge gaps remain. Advances are limited in part due to the lack of informative animal models. The authors recently reported on a method of DED induced by injecting all orbital lacrimal gland (LG) tissues with the lectin concanavalin A. Here, we report a novel model of aqueous-deficient DED based on the surgical resection of all orbital LG (dacryoadenectomy) tissues. Both methods use rabbits because of their similarity to human eyes in terms of the size and structure of the ocular surface. One week after removal of the nictitating membrane, the orbital superior LG was surgically removed under anesthesia, followed by removal of the palpebral superior LG, and finally removal of the inferior LG. Dacryoadenectomy induced severe DED, evidenced by a marked reduction in the tear break up time test and the Schirmer&#39;s tear test, and significantly increased tear osmolarity and rose bengal staining. Dacryoadenectomy-induced DED lasted at least eight weeks. There were no complications and animals tolerated the procedure well. The technique can be mastered relatively easily by those with adequate surgical experience and appreciation of the relevant rabbit anatomy. Since this model recapitulates the features of human aqueous-deficient DED, it is suitable for studies of ocular surface homeostasis, DED, and candidate therapeutics.

A novel approach is presented to induce chronic dry eye disease in rabbits by surgically removing all orbital lacrimal glands. This method, distinct from those previously reported, produces a stable, reproducible model of aqueous deficient dry eye well suited to study tear physiology and pathophysiology and ocular therapeutics.

Dry eye disease (DED) is a complex disease with multiple etiologies and variable symptoms, having ocular surface inflammation as its key pathophysiologic ...

Intratracheal Administration of Dry Powder Formulation in Mice

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper introduces a noninvasive method of intratracheal delivery of dry powder formulation in mice. A dry powder loading device that consists of a 200 &#181;L gel loading pipette tip connected to an 1 mL syringe via a three-way stopcock is presented. A small amount of dry powder (1-2 mg) is loaded into the pipette tip and dispersed by 0.6 mL of air in the syringe. Because pipette tips are disposable and inexpensive, different dry powder formulations can be loaded into different tips in advance. Various formulations can be evaluated in the same animal experiment without device cleaning and dose refilling, thereby saving time and eliminating the risk of cross-contamination from residual powder. The extent of powder dispersion can be inspected by the amount of powder remaining in the pipette tip. A protocol of intubation in mouse with a custom-made light source and a guiding cannula is included. Proper intubation is one of the key factors that influences the intratracheal delivery of dry powder formulation to the deep lung region of the mouse.

Dry powder formulations for inhalation have great potential in treating respiratory diseases. Before entering human studies, it is necessary to evaluate the efficacy of the dry powder formulation in preclinical studies. A simple and noninvasive method of the administration of dry powder in mice through the intratracheal route is presented.

In the development of inhalable dry powder formulations, it is essential to evaluate their biological activities in preclinical animal models. This paper ...

Platelet-Rich Plasma Lysate for Treatment of Eye Surface Diseases

Various ocular surface diseases are treated with blood-derived eye drops. Their use has been introduced in clinical practice because of their metabolite and growth factor content, which promotes eye surface regeneration. Blood-based eye drops can be prepared from different sources (i.e., whole blood or platelet apheresis donation), as well as with different protocols (e.g., different dilutions and freeze/thaw cycles). This variability hampers the standardization of clinical protocols and, consequently, the evaluation of their clinical efficacy. Detailing and sharing the methodological procedures may contribute to defining common guidelines. Over the last years, allogenic products have been diffusing as an alternative to the autologous treatments since they guarantee higher efficacy standards; among them, the platelet-rich plasma lysate (PRP-L) eye drops are prepared with simple manufacturing procedures. In the transfusion medicine unit at AUSL-IRCCS di Reggio Emilia, Italy, PRP-L is obtained from platelet-apheresis donation. This product is initially diluted to 0.3 x 109 platelets/mL (starting from an average concentration of 1 x 109 platelets/mL) in 0.9% NaCl. Diluted platelets are frozen/thawed and, subsequently, centrifuged to eliminate debris. The final volume is split into 1.45 mL aliquots and stored at &#8722;80 &#176;C. Before being dispensed to patients, eye drops are tested for sterility. Patients may store platelet lysates at &#8722;15 &#176;C for up to 1 month. The growth factor composition is also assessed from randomly selected aliquots, and the mean values are reported here.

Platelet lysates represent an emerging tool for the treatment of ocular surface diseases. Here, we propose a method for the preparation, dispensation, storage, and characterization of platelet lysate collected from platelet donors.

Various ocular surface diseases are treated with blood-derived eye drops. Their use has been introduced in clinical practice because of their metabolite ...

Comparing Objective Conjunctival Hyperemia Grading and the Ocular Surface Disease Index Score in Dry Eye Syndrome During COVID-19

The incidence of dry eye syndrome (DES) has increased due to wearing masks, utilizing digital devices, and working remotely during the pandemic. A survey was conducted during the COVID-19 pandemic to determine the prevalence of dry eye syndrome. A cross-sectional study investigated how prevalent DES is during COVID-19 in healthy patients aged 20-45 in the United States. An Ocular Surface Disease Index (OSDI) questionnaire was given to 40 individuals remotely from October 31, 2021, to December 1, 2021. The AOS and the OSDI survey were used to evaluate DES. The subjects were 29 years old on average (SD 14.14), with 23 males (57.5%) and 17 females (42.5%). According to the OSDI survey, low DES, moderate DES, and severe DES had prevalence rates of 15%, 77.5%, and 7.5%, respectively. White (W) people represent 50% of the population, while African Americans (AA) represent 35%, Asians represent 7.5%, and Hispanics represent 7.5%. Mild DES affected 77.5% of subjects, with 64.50% males and 35.50% females. According to the AOS objective grading system, mild (M) DES, moderate (MO) DES, and severe (S) DES had prevalence rates of 40%, 12.5%, and 15%, respectively. Linear regression was used to compare the two grading systems, and it demonstrated a strong relationship between the two grading systems.

The present protocol describes the cross-sectional research performed on 40 healthy subjects between the ages of 20 and 45 to assess the prevalence of dry eye syndrome (DES) during COVID-19. The OSDI survey evaluated DES, and the advanced ophthalmic systems (AOS) software was used to assess limbal redness.

The incidence of dry eye syndrome (DES) has increased due to wearing masks, utilizing digital devices, and working remotely during the pandemic. A survey ...