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VIDEO: Novaliq seeks entry into US dry eye market

Posted by australiandryeye on April 17, 2018 at 1:20 AM Comments comments (0)

WASHINGTON ― At the Ophthalmology Innovation Summit at ASCRS here, Bernhard Günther, president of Novaliq, discusses the company’s efforts to enter the U.S. market, principally in treating dry eye disease, by establishing an office in Cambridge, Massachusetts.


https://www.healio.com/ophthalmology/ophthalmic-business/news/online/%7B786f9329-28c4-4580-b18f-94083f661da4%7D/video-novaliq-seeks-entry-into-us-dry-eye-market

SiteOne Therapeutics Announces Abstract Presentation At the Association for Research in Vision and Ophthalmology (ARVO)

Posted by australiandryeye on March 27, 2018 at 6:30 AM Comments comments (1)

BOZEMAN, Montana, March 26, 2018 /PRNewswire/ -- SiteOne Therapeutics, Inc., today announced a presentation at the Association for Research in Vision and Opthalmology (ARVO) meeting in Honolulu, Hawaii, April 29 to May 3, 2018.


The abstract will present preclinical research using SiteOne's novel sodium ion channel blockers showing corneal anesthesia, penetration into the ocular structures, and excellent tolerability after topical administration. The study was conducted to inform development of a novel drug candidate to treat ocular pain associated with dry eye syndrome.


Accepted ARVO abstract is listed below:


Delwig, A. et al, "Evaluation of Selective NaV 1.7 Inhibitors for the Treatment of Ocular Pain" Abstract # 2908312, Poster Presentation.


About Ocular Pain Associated with Dry Eye Syndrome


Dry eye syndrome is a clinical diagnosis that encompasses a broad range of distinct conditions with unique etiologies that share signs and symptoms, the most common of which are sensations of burning, stinging, itching or grittiness in the eyes. The objective of our program is to develop a topical ophthalmic analgesic to safely and effectively treat ocular discomfort associated with the diagnosis of dry eye. This product would also be useful for treating other types of ocular pain, such as post-surgical pain and pain associated with acute corneal injuries or abrasions.


Existing therapeutics for dry eye include topical cyclosporine (Restasis) and lifitegrast (Xiidra). Both drugs address the inflammatory component of the disease by inhibiting activation of T-cells, however signs and symptoms of dry eye frequently persist.

 

The objective of our program is to advance a topical ophthalmic analgesic that reduces ocular discomfort associated with dry eye by targeting a voltage-gated sodium channel in the cornea, NaV1.7, and reducing corneal pain. Our product has the potential to be broadly effective in the ~30 million Americans suffering from dry eye regardless of the etiology because it addresses the discomfort rather than the heterogeneous physiologic cause. The analgesic would complement therapeutics that reduce inflammation or improve tear film, allowing the patient to be comfortable over weeks to months required for these therapies take effect. It would also be a useful treatment for postoperative pain following certain surgical procedure and acute ocular injuries, such as corneal abrasion.

 

About SiteOne Therapeutics, Inc.


SiteOne Therapeutics is a biotechnology company headquartered in Bozeman, Montana with a research laboratory in the South San Francisco, California. Since its inception, SiteOne has been dedicated to developing novel pain therapeutics to safely, effectively and efficiently treat acute and chronic pain without the limitations of existing pain therapies, such as NSAIDs or opioids. The company's therapeutic candidates are highly selective sodium ion channel 1.7 (Naᵥ1.7) inhibitors based on naturally occurring small molecules. Given the urgent need for new, non-opioid solutions for managing pain, SiteOne is focused on advancing its lead product candidates for multiple therapeutic applications.



SOURCE SiteOne Therapeutics


https://www.prnewswire.com/news-releases/siteone-therapeutics-announces-abstract-presentation-at-the-association-for-research-in-vision-and-ophthalmology-arvo-300618992.html

Biomedical startup AesculaTech is creating a new, more patient-friendly drug delivery system

Posted by australiandryeye on March 26, 2018 at 8:10 AM Comments comments (0)

“Reverse chocolate” — that’s how AesculaTech co-founder and chief science officer Niki Bayat describes the material created by its proprietary technology. Chocolate is solid until heated, when it melts deliciously into liquid. AesculaTech’s material, on the other hand, is a liquid at low temperatures, turns into a gel when heated and then reaches its final, solid state at body temperature. (If you are having a hard time visualizing the process or are distracted by thoughts of dessert, there’s a gif below that shows it being injected into a 37 degree Celsius water bath).

 

By changing the composition of the material, AesculaTech is able to control the temperature at which it transitions into different states. While the liquid is transforming into a gel, different compounds, including medications, can be added to it. Bayat and co-founder Andrew Bartynski, who are in Y Combinator’s latest startup batch, say it has a wide range of potential applications, including pharmaceuticals, medical devices, cosmetics and textiles.

 

First, the material is being used in a treatment for dry eye syndrome. AesculaTech’s founders say the condition affects more than 20 million people in America, who collectively spend $3.5 billion a year treating symptoms that can include a burning, scratchy sensation, discharge and impaired vision. Prescription treatments like Restasis and Xiidra can take weeks or even months to reach full effectiveness, while over-the-counter eye drops bring only minutes of relief and need to be reapplied constantly. AesculaTech’s treatment, however, is designed to be administered by a doctor during a quick, in-office procedure and last for about a year. It is slated to be commercially available by 2019.

 

Bayat and Bartynski, AesculaTech’s chief executive officer, met in 2012 while doing graduate work in chemical engineering at the University of Southern California and discovered a shared interest in unique classes of materials. As graduation drew closer, they began to think of what they wanted to do next.

 

“One day I was talking to my dad and I heard from him that he’d been diagnosed with glaucoma, but because he’d had heart surgery, he couldn’t have another one,” says Bayat. “I kept thinking there should be a better way to treat glaucoma and so I started working on this project with Andrew and a few other people.”

 

The team decided to focus on dry eye syndrome first because it is easier to treat, but they plan to work on glaucoma medication in the future. The treatment starts off as an injectable liquid that is inserted into the patient’s tear duct by a doctor. It turns into a solid after raising to body temperature, forming a tiny plug that keeps tears from draining away from the surface of the eye.

 

AesculaTech has already performed pre-clinical animal trials that show its dry eye treatment creates statistically significant increases in tears on eyes and are preparing for human trials to bring it closer to approval from the Food and Drug Administration.

 

Because it only needs to be applied once a year, the treatment addresses another important health issue: medication compliance. Many patients don’t stick to drug regimens for chronic conditions as directed by their physicians even though it reduces the efficacy of their medicines. In the case of antibiotics, patient non-compliance can also impact public health by increasing bacterial resistance. As it branches out beyond ophthalmic treatments, Bayat and Bartynski hope their technology will form the foundation of a new way of taking medication that is more realistic for patients to follow.

 

“To allow people to get the treatment they need without having to interact with medication on a daily basis is hugely valuable because you deliver the treatment to them continuously so they don’t have to interrupt their daily life or be bound to an eye drop or pill pack,” says Bartynski.

 

“It’s not only about the treatment of dry eye or glaucoma,” adds Bayat. “We are thinking of a platform for drug delivery technology.”

 

AesculaTech’s founders say the technology can also be used to create materials for a wide range of products, like cosmetics and smart textiles that are temperature responsive. The startup’s plan is to form partnerships with companies, license their technology and help them bring new products to market. The material hasn’t been tested for food products yet, but Bayat and Bartynski say they haven’t seen any indications that it isn’t edible, so reverse chocolate may one day be more than just a simile.

https://techcrunch.com/2018/03/19/biomedical-startup-aesculatech-is-creating-a-new-more-patient-friendly-drug-delivery-system/

Grafton Optical to launch new dry eye products

Posted by australiandryeye on March 26, 2018 at 8:05 AM Comments comments (0)

Grafton Optical will launch SBM Sistemi’s Ocular Surface Analyser and the i-Pen Tear Film Osmolarity System by i-Med Pharma at Optrafair (14–16 April, Birmingham NEC).


The i-Pen is a hand-held electronic device designed to detect and indirectly measure the elevated tear film osmolarity levels associated with dry eye disease.


The in-practice screening device can be used for patients presenting with dry eye symptoms, as well as pre and post-surgery patients.


SBM Sistemi’s Ocular Surface Analyser provides a full assessment of the ocular surface through a combination of tests for dry eye disease.


It analyses the Meibomian glands and enables the practitioner to carry out tear film interferometry screening.


The integrated software allows the user to analyse the functional and non-functional areas, and to evaluate the extension of the affected areas.


For further information, visit the Grafton Optical website.

https://www.aop.org.uk/ot/industry/equipment-and-suppliers/2018/03/23/grafton-optical-to-launch-new-dry-eye-products

TopiVert Publication Highlights the Potential of Narrow Spectrum Kinase Inhibitors in Dry Eye Disease and Supports Successful Clinical Proof-Of-Concept Study with TOP1630

Posted by australiandryeye on March 26, 2018 at 8:05 AM Comments comments (0)

TopiVert Publication Highlights the Potential of Narrow Spectrum Kinase Inhibitors in Dry Eye Disease and Supports Successful Clinical Proof-Of-Concept Study with TOP1630


London, UK, 22 March 2018: TopiVert Pharma Ltd ("TopiVert" or the "Company"), a clinical-stage biotechnology company developing Narrow Spectrum Kinase Inhibitors (NSKIs) as novel, locally-acting medicines for the treatment of chronic inflammatory ocular and gastrointestinal diseases, today announces the publication of "Narrow Spectrum Kinase Inhibitors Demonstrate Promise for the Treatment of Dry Eye Disease and Other Ocular Inflammatory Disorders" in Investigative Ophthalmology & Visual Science (IOVS, March 2018, Vol. 59, 1443-1453), a peer-reviewed journal for the dissemination of results from laboratory and clinical ophthalmic and vision research. 


The publication presents the results of a collaboration with the group of Dr Suzanne Hagan, Lecturer in Vision Sciences at Glasgow Caledonian University, which demonstrated upregulated expression of NSKI targets, pivotal enzymes in inflammatory signalling cascades, in DED patients along with key inflammatory cytokines and matrix metalloproteinase-9 (MMP-9). TOP1362, an NSKI specifically designed to inhibit these target kinases, potently reduced cytokine release in cellular models of innate and adaptive immunities. These reductions in inflammatory cytokine release also translated into an in vivo setting, where TOP1362 attenuated the increase in inflammatory cell infiltration and ocular cytokine levels in a preclinical inflammatory eye model with efficacy comparable to that of high potency steroid dexamethasone.


Inflammation is a core driver of DED. TopiVert believes that breaking the inflammatory cycle with NSKIs will provide efficacy superior to that of existing DED therapies with good tolerability. In this regard, in November 2017, TopiVert announced compelling results with TOP1630, an NSKI obtained following optimisation of TOP1362, in a Phase 1/2a proof-of-concept (POC) study in DED. TOP1630 delivered statistically significant improvements compared to placebo across multiple sign and symptom endpoints starting at day 15, the first study assessment point. Importantly, this NSKI provided excellent safety and placebo-like tolerability and comfort profiles, in contrast to currently marketed products, including steroids.


Dr Victor Perez, Professor of Ophthalmology at Duke University, said: "Further to the exciting TOP1630 clinical POC study results announced last year, the IOVS article by Hagan and co-workers highlights the novel NSKI mechanism of action as being one with the potential to provide compelling, steroid-like, efficacy in DED and also reveals biomarker targets for possible evaluation in the Phase 2b/3 study planned for later this year. The ability to block a narrow range of multiple kinases safely with a single compound is very attractive and offers much potential in treating inflammatory and non-inflammatory diseases of the eye."


Steve Webber, TopiVert's Chief Scientific Officer, added: "We have previously shown that targeted multi-kinase inhibition provides broad efficacy in both the innate and adaptive immune responses, giving rise to significant advantages over "single" kinase approaches. The IOVS article highlights the potential utility of NSKIs for treating DED. We are pleased to have translated the preclinical research described in the article into the convincing efficacy seen in the TOP1630 clinical POC study and look forward to commencing late-stage development of this exciting agent in an area of significant unmet medical need."


https://globenewswire.com/news-release/2018/03/22/1444621/0/en/TopiVert-Publication-Highlights-the-Potential-of-Narrow-Spectrum-Kinase-Inhibitors-in-Dry-Eye-Disease-and-Supports-Successful-Clinical-Proof-Of-Concept-Study-with-TOP1630.html

Yuyu to start clinical trials on dry eye treatment

Posted by australiandryeye on March 26, 2018 at 8:05 AM Comments comments (0)


Yuyu Pharmaceuticals said Thursday that it has received approval from the Ministry of Food and Drug Safety to go ahead with domestic phase 1 clinical trials for YY-101, a peptide-based dry eye treatment.


 

Dry eye syndrome is a common eye condition, in which the eye surface gets damaged due to insufficient tear production or excessive tear evaporation. The number of patients suffering from the disorder is on the rise because of the increase of computers, smart devices, air conditioners, and heaters.


Inje University Paik Hospital plans to conduct a randomized, double-blind and placebo-controlled phase 1 clinical trials on 28 healthy adult male volunteers to test the drug’s safety, tolerability, and pharmacokinetic properties. The hospital also conducted pre-clinical trials before the approval.


The Korea Evaluation Institute of Industrial Technology under the Ministry of Trade, Industry and Energy selected the drug as a promising bio-IP business promotion project.


“YY-101 is a new peptide-based drug that has confirmed its efficacy and safety in preclinical testing,” said Baek Tae-gon, head of research at the company. “The company plans to accelerate the speed of new drug development with the phase 1 clinical trial approval.”


The ministry also approved phase 3 clinical trials on YY-201, the company’s benign prostatic hypertrophy combined treatment, on March 9.


[email protected]


<© KBR , All rights reserved.>


http://m.koreabiomed.com/news/articleView.html?idxno=2857

Kala Pharmaceuticals Reports Fourth Quarter and Full Year 2017 Financial Results

Posted by australiandryeye on March 26, 2018 at 8:00 AM Comments comments (0)

Reported topline results from two Phase 3 clinical trials of KPI-121 0.25% - STRIDE 1 and STRIDE 2 – in patients with dry eye disease.


Achieved statistical significance for the primary sign endpoint of conjunctival hyperemia at Day 15 in the ITT population in both trials.


Achieved statistical significance for the primary symptom endpoint of ocular discomfort severity at Day 15 in the ITT population in STRIDE 1 with a trend towards a treatment effect in STRIDE 2.


Achieved statistical significance for the second primary symptom endpoint of ocular discomfort severity at Day 15 in patients with a more severe baseline discomfort in STRIDE 1 with a strong trend towards a treatment effect observed for the same endpoint in STRIDE 2.


Positive treatment effects were also observed for symptom endpoint of ocular discomfort severity in the ITT population at Day 8 in both trials, which was a key pre-specified secondary endpoint.


KPI-121 0.25% was well-tolerated in both trials with elevation in intra-ocular pressure, a known side effect with topical corticosteroids, similar to placebo.


Additional analyses of STRIDE 1, STRIDE 2 and Phase 2 data


Kala conducted additional analyses on a post-hoc basis to better understand the data on KP1-121 0.25% for patients with dry eye disease.


Phase 2 ocular discomfort data using the analysis method defined in the Phase 3 statistical analysis plan: Kala observed a positive treatment effect for ocular discomfort at day 15 (p=0.0489) using this analysis method. Additionally, a similar magnitude of effect was observed in the Phase 2 trial as observed in STRIDE 1 (5.27 mm and 5.44 mm differences vs. vehicle, respectively).


Pooled ITT populations from STRIDE 1 and STRIDE 2: A positive treatment effect was observed for the primary symptom endpoint of ocular discomfort at day 15 (p<0.0001) in this pooled population. The pooled results in 2 exploratory analyses in subgroups defined by geographical regions of east and west achieved p-values of 0.0071 and 0.0021 respectively and north and south achieved p-values of 0.0002 and 0.0176, respectively.

Effect on ocular discomfort on each of the days between days 8 and 14 in STRIDE 1 and STRIDE 2 using the analysis that was pre-specified for day 15: P-values of less than 0.002 were observed for all days during that time period in STRIDE 1, and p-values less than 0.05 were observed on 6 of the 7 days during that time period in STRIDE 2.


https://www.businesswire.com/news/home/20180326005323/en/Kala-Pharmaceuticals-Reports-Fourth-Quarter-Full-Year

Eyelove, the sequel: Jennifer Aniston reprises her starring role in Shire's dry eye awareness push

Posted by australiandryeye on March 24, 2018 at 8:00 AM Comments comments (0)


Time for more eyelove, and more Jennifer Aniston. Since the Shire disease awareness campaign launched more than a year ago, the eye community told Shire they wanted more Jen. So the pharma obliged, with original celebrity spokesperson Aniston even more front and center in its just-launched “eyelove” creative.


Aniston kicked off the eyelove campaign in fall 2016 in ads, telling the story of how she found out she had dry eye. But the latest work is meant to showcase even more of her personality.


In the new TV ad, Aniston plays the pop culture game “This or That” with a narrator as she demonstrates the choices. Flip-flops or boots? Smoky or natural eye? Calling or texting? Puppies or kitties? And finally—dry eyes or artificial tears?

Aniston stops and addresses the camera, “Wait, that’s a trick question. Because they can both get in your way. That’s why it is super important to chat with your eye doctor if you’re using artificial tears a lot and your eyes still feel dry.”


The new TV ad debuted on the Golden Globe awards Sunday. This next phase of the eyelove campaign also includes print, digital, social and in-pharmacy executions. Shire’s ad agency for eyelove is Digitas Health.

“Jen is a big engagement vehicle for us. People really relate to her, and we want to pull that through in all of our channels,” said Vic Noble, global head of brand value at Shire.


"Jen kicked off the momentum we wanted in tapping into that girlfriend voice," Noble added in an interview. "We want to pull that through the entire eyelove campaign.”


As part of that girlfriend-voice strategy to reach women, Shire and Digitas also created an original online social series last year, “In My Bag,” in which two women meeting each other for the first time switch bags and go through their contents. One of each pair has been diagnosed with dry eye disease, while the other is symptomatic. The lighthearted, chatty and often funny short videos each include some discussion of the problems and symptoms of dry eye, but fit into the overall theme of girlfriend chats and sharing stories.


Typical conversations include observations and commonalities. For instance, in one of the six videos already produced with two women named Marina and Danielle, Danielle is looking through Marina’s wallet and notes, “You like your coupons.” Maria interjects, “I feel like I’m turning into my mother,” and Danielle agrees, “Aren’t we all?”


The eyelove campaign has been a success with both its consumer and professional customers. Shire was new to the dry eye space when eyelove launched, but after a year, Shire research found that more than 90% of healthcare professionals connected the eyelove campaign to Shire. During 2017, the dry eye market also grew by 25%, she said. And even though the target audience is women 40-plus who are symptomatic, men have responded well to the campaign, too.


“Eyelove is about disease awareness, but in our minds, it’s really around disease engagement. We want people to engage with our content, engage with our platform and most importantly, drive engagement with their doctors,” Noble said.

Shire joined the market in 2016 with its dry eye treatement Xiidra, taking on the incumbent, Restasis from Allergan, although the two products are approved for different indications. Xiidra is approved specifically for dry eye, while Restasis is indicated for increasing tear production only. Shire marketing includes a separate branded marketing campaign for Xiidra with work, also from Digitas Health, that uses the "ii" in the drug’s name to create visual plays on words.


https://www.fiercepharma.com/marketing/shire-taps-actress-jennifer-aniston-again-for-second-round-eyelove-campaign

Novaliq begins phase 2 dry eye trial of NOV03

Posted by australiandryeye on March 24, 2018 at 8:00 AM Comments comments (0)

The first patient has been enrolled in the SEECASE phase 2 trial of NOV03 for the treatment of dry eye disease, Novaliq announced in a press release.

 

The multicenter, randomized, double-masked, saline-controlled study will evaluate the effect of NOV03 at both twice daily and four times a day.

NOV03 is designed to penetrate further into the meibomian glands, potentially dissolving meibomian lipids and helping to improve gland functionality, the release said.


“Earlier studies have demonstrated a highly favorable safety and efficacy profile in patients with DED, particularly for evaporative DED and [meibomian gland dysfunction],” Sonja Krösser, PhD, vice president of clinical development at Novaliq, said in the release.


Top-line data are expected in the second half of the year.

https://www.healio.com/ophthalmology/cornea-external-disease/news/online/%7B8a330a45-b51d-4efb-9451-2d08a4c048be%7D/novaliq-begins-phase-2-dry-eye-trial-of-nov03

Bausch + Lomb Receives FDA Approval of LUMIFY

Posted by australiandryeye on March 24, 2018 at 8:00 AM Comments comments (0)

The Only Over-The-Counter Eye Drop With Low-Dose Brimonidine For The Treatment Of Eye Redness


Clinical Studies Showed 95% Symptom Improvement At One Minute, And Reduced Redness For Up To Eight Hours


LAVAL, Quebec, Dec. 22, 2017 /PRNewswire/ -- Bausch + Lomb, a leading global eye health company and wholly owned subsidiary of Valeant Pharmaceuticals International, Inc. (NYSE: VRX and TSX: VRX) ("Valeant"), today announced that the U.S. Food and Drug Administration (FDA) has approved LUMIFY™ (brimonidine tartrate ophthalmic solution 0.025%) as the first and only over-the-counter (OTC) eye drop developed with low-dose brimonidine tartrate for the treatment of ocular redness. Brimonidine, which was first approved by the FDA in 1996 for intraocular pressure (IOP) reduction in glaucoma patients, is available at higher doses in prescription eye care products.


"With today's approval of LUMIFY, consumers have a new and unique treatment option to relieve red, irritated eyes," said Joseph C. Papa, chairman and CEO of Valeant. "LUMIFY is the first and only OTC eye drop with low-dose brimonidine, which has been clinically proven to be safe and effective since its initial approval as a prescription medication in 1996. We expect LUMIFY will be available for purchase in major retailers in the second quarter of 2018."


Ocular redness is a common condition that can be caused by inflammation of almost any part of the eye. With frequent use, non-selective redness relieving eye drops that constrict blood vessels in the eye can result in users developing a tolerance or loss of effectiveness, as well as rebound redness. In contrast, low-dose brimonidine, the active ingredient in LUMIFY, selectively constricts veins in the eye, increasing the availability of oxygen to surrounding tissue, thereby reducing the potential risk of these side effects.


"Patients with eye redness and irritation can experience negative social connotations, which may impact daily life," said Dr. Paul Karpecki, OD, FAAO, Director of Corneal Services at Kentucky Eye Institute. "Having a drop that reduces redness without the side effects of rebound hyperemia or tachyphylaxis, which may lead to overuse and potential corneal toxicity, is a very exciting option that I look forward to recommending to my patients."


For more information, please visit www.bausch.com.


The brimonidine tartrate ophthalmic solution 0.025% product was licensed by Eye Therapies, Inc. to Bausch + Lomb.


https://www.prnewswire.com/news-releases/bausch--lomb-receives-fda-approval-of-lumify--the-only-over-the-counter-eye-drop-with-low-dose-brimonidine-for-the-treatment-of-eye-redness-300575106.html

Biotech with treatment for chronic dry eye disease tied to diabetes raises seed capital

Posted by australiandryeye on March 24, 2018 at 8:00 AM Comments comments (0)

Biotech startup Ocunova, a spin-out from the Penn State University College of Medicine, has closed a fresh round of seed funding to support clinical trials for a treatment aimed at a chronic dry eye condition related to diabetes.


The treatment enlists a drug already approved by the FDA to manage alcohol and opioid dependence called Naltrexone. The company noted on its website that more than 3 million diabetic patients experience chronic dry eye in the U.S.


The $500,000 seed round comes from two funding sources supported by Pennsylvania: Life Sciences Greenhouse of Central Pennsylvania (LSGCP) and a branch of the state economic development arm Ben Franklin Technology Partners/Central and Northeastern Pennsylvania. Based in Harrisburg, LSGCP functions as a technology transfer group and also works with research institutions, medical centers, economic development agencies, and companies to identify needs and opportunities in life sciences. It is one of three regional biotechnology research centers that were created using funds from the state’s Tobacco Settlement Fund.


In a statement, CEO Michael Shine explained why he regards his company’s treatment as a gamechanger for the disease.


“Current treatments are limited to either over-the-counter eye drops that provide temporary relief to the eye or two prescription, anti-inflammatory medications which have delayed onset of action, variable efficacy and side effects which limit compliance. There are no treatments approved for diabetic DES. Ocunova’s drug candidate, OCU-001, is designed to affect the underlying cause of DES, which is a novel approach.”


Another group that focused on treatments for dry eye disease related to specific condition is TearSolutions. Founded by cellular biology professor Gordon Laurie with the University of Virginia and led by Tom Gadek, the company is developing a treatment called Lacripep. The first indication is for people with the autoimmune disease Sjögren’s syndrome. The drug, currently in clinical trials, is a topical eye drop that seeks to eliminate inflammatory triggers by restoring the natural basal tearing mechanism and health of cells in contact with tears, according to a description on the group’s website. This includes restoration of the nerves on the cornea of the eye, which signal the brain to produce more tears. It also stabilizes the tear film that in dry eye is very unstable. Last month, TearSolutions received backing from UVA Licensing and Ventures Group‘s Seed Fund.


There are also a fair few life science companies that have developed dry eye disease treatments for the wider population. One, TearScience, was acquired by Johnson & Johnson last year.


https://medcitynews.com/2018/02/biotech-treatment-chronic-dry-eye-disease-tied-diabetes-raises-seed-capital/

Aldeyra Therapeutics Inks Collaboration Deal with Johnson & Johnson to Develop Anti-inflammatory Therapies

Posted by australiandryeye on March 24, 2018 at 7:55 AM Comments comments (0)

By Mark Terry


Based in Lexington, Massachusetts, Aldeyra Therapeutics just signed a collaboration research deal with Janssen Research & Development, a Johnson & Johnson company.


The companies will work together to develop drugs that sequester pro-inflammatory aldehyde mediators. This is a new class of therapeutic targets. Aldeyra’s lead program is reproxalap, a first-in-class drug candidate that has shown anti-inflammatory activity in four Phase II clinical trials. Reproxalap is being evaluated for dry eye disease and other types of ocular inflammation. The agreement will advanced the existing analogs of reproxalap to treat inflammatory diseases.


Aldeyra will work with Janssen on research activities, which will be overseen by a joint scientific review committee. For a limited but unannounced period, Janssen will keep an option to negotiate an exclusive license to compounds that come out of the relationship.


“As we are committed to the development of novel therapeutic product candidates for autoimmune and other diseases characterized by systemic inflammation, we are pleased to partner with Janssen, a world leader in the discovery and development of therapeutics for inflammatory diseases,” said Todd Brady, president and chief executive officer of Aldeyra, in a statement.


No specific financial details for the agreement were released.


On November 29, 2017, the company presented new statistical analyses of its Phase II trial of reproxalap to the American Uveitis Society held at the American Academy of Ophthalmology 2017 Annual Meeting. The data showed formal statistical non-inferiority of 0.5% reproxalap ophthalmic solution compared to Pred Forte, a topical ocular corticosteroid, in reducing anterior chamber inflammatory cell count. The combination of reproxalap and twice-daily Pred Forte also was non-inferior to Pred Forte monotherapy four times a day.


“The use of corticosteroid therapy for the treatment of ocular inflammation is hampered by ophthalmic toxicity, including cataract formation, secondary infection, viral reactivation, delayed wound healing and elevated intraocular pressure that can cause irreversible glaucomatous optic atrophy,” said John Sheppard, professor of Ophthalmology, Eastern Virginia Medical School, who gave the presentation, in a statement. “Reproxalap could represent a welcome addition to the topical therapeutic options available to practitioners who treat noninfectious anterior uveitis, a severe inflammatory disease which can lead to permanent vision loss.”


And on January 30, 2018, Aldeyra announced that it had enrolled its first patient in a Phase IIb trial of reproxalap for dry eye disease. The trial will test two concentrations of the drug over 12 weeks in 300 patients with moderate dry eye disease.


“Existing therapy for dry eye disease, a common inflammatory condition that leads to persistently disturbing ocular irritation, is generally considered by physicians and patients to be inadequate, but represents one of the largest ophthalmic markets worldwide,” said Brady, in a statement. “Based on the positive results from the Phase IIa dry eye disease clinical trial with our topical ocular product candidate reproxalap announced in September 2017, we are pleased to begin enrolling our Phase IIb clinical trial, and expect to report results in the second half of this year.”


It seems that the work and results with reproxalap is what attracted J&J to the company and that category of drug.


BioSpace source:

https://www.biospace.com/article/aldeyra-therapeutics-inks-collaboration-deal-with-johnson-and-johnson-to-develop-anti-inflammatory-therapies


http://www.pharmalive.com/aldeyra-therapeutics-inks-collaboration-deal-with-johnson-johnson-to-develop-anti-inflammatory-therapies/

Key U.S. Dry Eye Patent Issued to RegeneRx

Posted by australiandryeye on March 24, 2018 at 7:55 AM Comments comments (0)

ROCKVILLE, Md., Feb. 22, 2018 /PRNewswire/ -- RegeneRx Biopharmaceuticals, Inc. (OTCQB: RGRX)("the Company" or "RegeneRx"), a clinical-stage drug development company focused on tissue protection, repair and regeneration, today announced that the U.S. Patent and Trademark Office (USPTO) has issued a patent for Thymosin beta 4 (Tβ4) for use in the treatment of dry eye syndrome. Tβ4 is the active pharmaceutical ingredient in RegeneRx's proprietary drug candidate, RGN-259, a first-in-class, preservative-free, eye drop designed for patients suffering from moderate to severe dry eye syndrome.


Dry eye syndrome is a multifactorial disease of the eye and its treatment with Tβ4 would represent a major step forward from current treatment options by promoting cell migration and proliferation, reducing inflammation and accelerating corneal epithelial growth, while offering a rapid patient response with no side effects.


Two Phase 3 dry eye trials (ARISE-1 and ARISE-2), sponsored by the Company's U.S. joint venture, ReGenTree LLC, have been completed in over 900 dry eye patients with clinically significant results. ReGenTree has scheduled a meeting with the FDA in April to discuss its clinical development and regulatory plans for RGN-259.


"This patent is very significant in that it is specifically focused on administering RGN-259, consisting of Tβ4 or certain of its fragments, for the treatment of dry eye syndrome in the U.S. This, as well as additional patents we expect to receive, further enhances our unique and proprietary position in this area," stated J.J. Finkelstein, RegeneRx's president and chief executive officer.


https://www.prnewswire.com/news-releases/key-us-dry-eye-patent-issued-to-regenerx-300602708.html

Shire licences Parion dry eye drug in $535m deal

Posted by australiandryeye on March 24, 2018 at 7:50 AM Comments comments (0)

Shire has agreed a licencing deal with Parion Sciences for a dry eye disease drug that bolsters its ophthalmic portfolio, a priority area for the Irish group.


Shire is paying $20m upfront for rights to P-321 a sodium channel (ENaC) inhibitor that is currently heading into a phase II trial, with another near-term development milestone of $20m on the cards in the near future. All told the deal could be worth up to $535m for North Carolina biotech Parion, while Shire adds to the pipeline behind its recently-approved dry eye disease therapy Xiidra (lifitegrast).


Xiidra became the first and only product approved in the US to treat both the signs and symptoms of dry eye disease when it got the go-ahead from the FDA last year, challenging a market for drug treatments currently dominated by Allergan’s $1.4bn product Restasis (cyclosporine). Shire’s drug was launched in August and had turned over $54m by the end of the year, adding another $39m in the first quarter with Shire claiming its product is now capturing 22% market share in the US.


P-321 is a topical formulation that is thought to work by blocking the absorption of tears, helping to keep the surface of the eye hydrated. That is a different mechanism of action to current drugs including Xiidra, which work by reducing inflammation in the eye. In a statement the two companies said the hope was that the drug could “address tear volume deficiency and promote ocular surface healing”.


Parion has already completed a phase I/II trial in 53 patients with mild-to-moderate dry eye disease with preliminary signs that it could improve symptoms.


“Ophthalmics is a continued focus for Shire, and the programme for P-321 will benefit from our development and commercial infrastructure and expertise,” said Shire’s CEO Flemming Ornskov. “This is an opportunity to apply our knowledge and experience from ophthalmics and dry eye disease for further innovation in this space.”


Dry eye is widespread but hard to define - in part because it can be caused by a range of factors and patients report symptoms from mild, temporary irritation through to chronic illness that can dramatically affect quality of life and even threaten sight.


Eyecare market research firm Market Scope estimates that new drugs will help drive the dry eye market from $3.4bn last year to nearly $4.5bn in 2021, with drugs taking a share alongside over-the-counter eyedrops and surgical devices.


In 2015 Shire bolstered its eyecare pipeline with the acquisition of Foresight Biotherapeutics for $300m, adding a late-stage treatment for bacterial and viral conjunctivitis.

http://www.pmlive.com/pharma_news/shire_licences_parion_dry_eye_drug_in_$535m_deal_1192208

Sylentis Initiates a Phase III Study for the Treatment of Dry Eye Syndrome

Posted by australiandryeye on March 24, 2018 at 7:40 AM Comments comments (0)

The pharmaceutical company Sylentis (PharmaMar Group) has announced the start of the first Phase III study, HELIX, with the investigational new drug, SYL1001 for the indication of dry eye syndrome. The company has agreed with the U.S. Food and Drug Administration (FDA) on plans for the Phase III clinical program, which is designed to support the submission of a New Drug Application (NDA). The company has received final, End-of-Phase II meeting minutes from the FDA.

 

SYL1001 is an advance in the development of innovative compounds in different therapeutic fields, through the novel technology of gene silencing, based on RNA interference (RNAi). In the HELIX study, more than 30 centers from 5 European countries (Spain, Germany, Estonia, Portugal and Italy) will participate with the objective of evaluating the effect of the ophthalmological solution SYL1001 for improvements in the signs and symptoms of dry eye syndrome in about 300 patients an area in which few therapeutic options exist today. SYL1001 is a compound based on RNAi being administered in the form of eye drops that block the synthesis of a receptor implicated in the pathology of dry eye syndrome.

 

Patients with dry-eye syndrome suffer the chronic loss of lubrication and hydration on the ocular surface. The risk of developing this disorder increases in 35% every decade thereafter[2]. Around the world, 344 million people suffer from this syndrome.

 

Dry eye syndrome is characteristic in people that live in developed countries and is caused by pollution, air conditioning, the use of contact lenses, refractive eye surgery or the continued use of computers. The most common symptoms of this pathology are burning, a constant itching, eye fatigue, dryness, blurred vision, the sensation of having a foreign body or eye pain[1], are some of the symptoms

 

As explained by Dr. Ana Isabel Jimenez, COO and Director of R&D at Sylentis, "the RNA interference on which we are working, could improve the signs and symptoms for patients that suffer from this syndrome, given that this compound could reduce the inflammatory parameters of the eye´s surface, could improve the quality of the tear and could reduce the ocular pain associated with dry eye syndrome. We consider that our molecule SYL1001 could be a very effective and important therapeutic alternative for these patients".

 

The company is working on the investigation of new treatments for ophthalmological and inflammatory illnesses. "Up to today, the line of work in which we have more rapidly advanced in is in ophthalmology, for the treatment of illnesses such as dry eye syndrome, glaucoma, ocular allergies and illnesses of the retina", added Jimenez.


https://www.pharmpro.com/news/2017/06/sylentis-initiates-phase-iii-study-treatment-dry-eye-syndrome

 

What is RNA Interference?

 

RNA interference is an innovative technology that looks for a reduction in the anomalous production of protein, silencing the RNA Messenger. The RNAi provides a step forward, as it provides a new mechanism of action to confront numerous pathologies[2]. Nowadays there are two marketed products based on this technology and there are several drugs in different phases of clinical development.

 

Pathologies, such as dry eye syndrome, are produced by an alteration in certain proteins. Through this technology, the production of proteins that take part in various pathologies could be decreased or very specifically controlled[3].

 

HELIX: A Clinical Trial Study

 

With the purpose of progressing in this field, Sylentis has begun the multicenter, random, controlled and double blind Phase III clinical trial in more than 30 hospitals in Spain, Germany, Estonia, Portugal and Italy. The trial, in which 300 patients are going to be enrolled will evaluate the efficacy of the product patented by Sylentis, SYL1001, in the treatment of the signs and symptoms of dry eye disease[4].

 

For more information about the clinical trial, click here.

 

Sources

 

The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye WorkShop (2007). Ocul Surf, 2007. 5(2): p. 75-92

Martínez T, Jimenez AI, Pañeda C. Short-interference RNAs: becoming medicines. EXCLI Journal, 2015;14:714-46

Pañeda C, González V, Martínez T, Ruz V, Vargas B and Jimenez AI. RNAi based therapies for ocular conditions. In Proceedings of the 11th ISOPT,2014, 25-30, Medimond, Bologna, Italy

Benitez-Del Castillo JM [https://www.ncbi.nlm.nih.gov/pubmed/?term=Benitez-Del-Castillo%20JM%5BAuthor%5D&cauthor=true&cauthor_uid=27893109], . Protocol No.: SYL1001_IV. EUDRACT No: 2016-003903-79. A double-masked study of SYL1001 in patients with moderate to severe dry eye disease (DED). HELIX Study (Phase III). Version 1.1: December 14th, 2016. Sylentis SAU-Pharma Mar Group

(Source: PR Newswire)

Ocugen's dry eye combination product shows positive phase 2 results

Posted by australiandryeye on March 24, 2018 at 7:40 AM Comments comments (0)

 

March 21, 2018

A phase 2 proof-of-concept clinical trial of OCU310, a combination of brimonidine tartrate and loteprednol etabonate, has shown meaningful improvements in patients with dry eye disease, according to an Ocugen press release.

 

Over a 12-week period, the randomized, multicenter, double-masked, placebo-controlled study met its primary endpoint of tolerability, the release said. In addition, it showed meaningful improvements related to dry eye signs and symptoms compared with placebo.

“We believe OCU310 can provide significant benefit to those suffering from dry eye disease, and we look forward to presenting the full results at a future academic meeting and discussing with the FDA in the coming months,” Daniel Jorgensen, MD, MPH, Ocugen chief medical officer, said in the release.

 

Phase 3 clinical studies of OCU310 are expected to begin in the third quarter of this year.

https://www.healio.com/ophthalmology/cornea-external-disease/news/online/%7Bb39d25e8-32f6-4624-ab34-603603fb1bbb%7D/ocugens-dry-eye-combination-product-shows-positive-phase-2-results

A London Biotech Aims to Overtake the Dry Eye Syndrome Market

Posted by australiandryeye on December 12, 2017 at 6:30 PM Comments comments (0)

TopiVert has released the results of a clinical trial that the company believes yielded “the best proof of concept data in dry eye syndrome.”


Based in London, the biotech company TopiVert is trying to enter the $3Bn market of dry eye syndrome with a drug with the potential to work better than the options currently available for patients with this condition.

 

“Most people are just not aware of the huge unmet medical need there is,” told me Ajay Duggal, CMO of TopiVert. “There are 40 million people with the disease in the US alone, and research has revealed dry eye syndrome impacts quality of life as much as angina.”

 

As he explains, many patients use over the counter eye drops to address the symptoms. But they do not target the cause of the disease, which is an inflammatory process. The leading prescription medicines are Allergan’s Restasis and Shire’s Xiidra, but both have limited efficacy and come with several side effects, including irritation of the eyes.

 

To address this situation, TopiVert is using a technology called narrow spectrum kinase inhibitors (NSKIs). “They work by targeting a range of kinases, which are molecules involved in the inflammatory response,” explains Nick Staples, CBO.

 

Kinase inhibitors are commonly used in cancer therapy, but they often cause side effects because kinases are involved in many other physiological processes. To avoid that, TopiVert targets a narrow selection of kinases and delivers the drug locally to the eye.

In a first, Phase I/IIa clinical trial where 60 patients were treated with either placebo or TopiVert’s therapy for dry eye syndrome, TOP1630, the company’s strategy seems to have proved successful. The therapy was as safe and well tolerated as the placebo. But most importantly, the efficacy data indicates the drug might be superior to what is currently on the market.

 

After 15 days, TOP1630 proved to show a significant improvement in several symptoms, including dryness, grittiness, ocular discomfort and pain, as well as on the signs physicians use to diagnose the disease, including measuring the deterioration of the cornea. These effects were further improved after 29 days on many of the measurements.

 

Duggal remarks that the results are particularly impressive given the consistency of effects across multiple symptoms and clinical signs. Furthermore, all these analyses were specified before running the trial, whereas most competitor studies have relied on post-hoc analysis to demonstrate an effect. Duggal is therefore confident that TopiVert will be able to reproduce these results in the next clinical trial. If the results are confirmed there, it would allow the company to seek approval. Something that could happen as soon as 2021.

https://labiotech.eu/dry-eye-syndrome-topivert/

Azura Ophthalmics receives Series B funding to create treatment for major cause of Dry Eye Disease

Posted by australiandryeye on December 4, 2017 at 10:15 PM Comments comments (0)

Melbourne, October 11, 2017 – Azura Ophthalmics has received US$16 million in Series B funding to develop treatments for Meibomian Gland Dysfunction (MGD) – the number one cause of Dry Eye Disease.


The funding from Brandon Capital’s Medical Research Commercialisation Fund (MRCF), TPG Biotech, OrbiMed and Ganot Capital, will allow the Israeli-Australian company to move into its next clinical stage in the development of novel treatments for MGD – an eye condition where the Meibomian Glands becomes dysfunctional which results in rapid evaporation of the tear film.


Meibomian glands reside in the upper and lower eyelids and are responsible for producing the oily layer that forms the outer most layer of a person’s tear film. This oil (lipid) layer, in conjunction with the watery layer of the tear film work together to maintain clear vision and ocular health. An intact lipid layer ensures tears do not evaporate and keeps the eyes moisturised and nourished. If this layer is disturbed, it leads to tears evaporating too quickly, drying out the ocular surface and resulting in damage to the front of the eye, discomfort, and a significant reduction in both quality of life and productivity.


As Azura Ophthalmics Chief Executive Officer Marc Gleeson explained, “Meibomian gland dysfunction is responsible for at least 70 per cent of dry eye cases and affects about 300 million people worldwide, yet despite significant efforts there are no pharmaceutical treatments available for this condition. Using our novel therapy, Azura has generated promising results in a phase 1 study in MGD sufferers. We are therefore optimistic that Azura’s treatment could one day provide the first effective treatment for MGD sufferers.”


MGD sufferers represent one of the largest and most underserved patient segments in ophthalmology. If left untreated MGD will alter the tear film, causing eye irritation, inflammation, and severe Dry Eye Disease (DED). Following initial clinical success with their lead compound, Azura Ophthalmics will undertake Phase 2a clinical testing of this new formulation in approximately 120 patients with MGD.


The Israeli-headquartered company was founded in Tel Aviv in 2014. All further research, clinical trials and the development of Azura’s Ophthalmics drug treatment will be undertaken in Australia.


MRCF Chief Executive Officer Dr Chris Nave noted, “Australia is an accepted world leader in medical research. However, historically a lack of investment funding in the life sciences sector has resulted in Australian medical discoveries leaving our shores to gain access to the capital required for further development. The government’s R&D tax incentive and the introduction of the $500 million-dollar Biomedical Translation Fund are addressing this problem and are attracting foreign life science companies like Azura Ophthalmics to Australia, stimulating the industry locally, creating jobs and keeping our talented clinicians and scientists, and their research, in Australia.”


Indeed, Sydney-based CEO, Marc Gleeson, is leveraging these incentives to bring innovation home. As Gleeson noted, “Australia has an attractive regulatory environment for early-stage clinical trials and the government’s R&D tax incentive, which sees eligible companies undertaking research and development in Australia, receive a refundable tax offset, helps preserve valuable capital. Azura Ophthalmics was established in Israel, which is highly-renowned for its innovation ecosystem. The Company is now looking to take advantage of Australia’s clinical research excellence and the incentives that support investment in Australian innovation”.


Through a combination of innovation from Azura Ophthalmics, the Australian government’s R&D tax incentive, and the Biomedical Translation Fund, Australia is now positioned to be at the forefront in developing innovative treatments for Meibomian Gland Dysfunction, the leading cause of dry eye disease, offering hope to hundreds of millions of people worldwide.


http://www.brandoncapital.com.au/blog/2017/10/azura-ophthalmics-receives-series-b-funding-to-create-treatment-for-major-cause-of-dry-eye-disease

Can cannabis succeed where other compounds have failed

Posted by australiandryeye on November 20, 2017 at 8:15 PM Comments comments (0)

Cannabinoids could have potential in a novel topical drug delivery vehicle to treat neuropathic dry eye pain.


The disconnect between signs and symptoms in dry eye disease is an intriguing clinical problem. Although we know quite a lot about the etiology of dry eye, the ideal structure of the tear film and how to diagnose and treat dry eye disease, there are still some patients who do not respond to treatment or who present complaining of severe symptoms that seem to be poorly correlated with clinical signs. Complaints may include a burning or stabbing sensation or a feeling of pressure in the eyes.


Many clinicians find these patients—and the chair time they consume—frustrating. But before dismissing them as “crazy,” it may help to consider whether they could be suffering from a different form of dry eye that is difficult to detect by traditional methods.


In 2009, Perry Rosenthal and colleagues observed what they presumed to be corneal neuralgia, which they termed “pain without stain” because of the paucity of corneal staining or other clinical signs.1 They speculated that the pain symptoms could be related to a neuropathic disorder, rather than to qualitative or quantitative tear film factors.


Later work by Rosenthal further elucidated how the nociceptive system—critical to vision when functioning properly, because it monitors and restores the optical tear film—could become dysfunctional.2 When this happens, the corneal nerves, the central trigeminal sensory network, and/or the pain organising centres in the brain escalate the eye’s natural ‘alarm system’, sending pain signals that are out of proportion to the physical insult (if indeed there is any injury at all).


Neuropathic dry eye pain may be triggered or exacerbated by ocular surgery, systemic conditions or even psychological distress.


The dry eye community has been increasingly interested in neuropathic dry eye. In fact, the new DEWS II definition of dry eye explicitly includes “neurosensory abnormalities” in the list of etiological factors in dry eye.3


A DEWS II subcommittee report on pain and sensation notes that long-term inflammation can alter neuron excitability, connectivity and impulse firing and that disturbances in ocular sensory pathways may ultimately lead to neuropathic pain.4 However, as yet, there are no dry eye therapies that specifically target neuropathic pain.

The role of cannabis


Cannabinoids and, in particular, tetrahydrocannabinol (THC, the main active ingredient in recreational marijuana) is of great interest in the treatment of neuropathic pain. Cannabinoid receptors are known to modulate pain and inflammation and are located throughout the eye, including the corneal epithelium and the retina; they are present on immune cells and may be involved in wound healing, as well.5 So, from a theoretical perspective there are a number of reasons to pursue the use of cannabinoids to treat dry eye.


And the time may be right to conduct such research now. Regulatory restrictions around the use of cannabinoids are being loosened, with more than half of U.S. states and several European countries now permitting the use of THC for medical purposes.


In Germany, where I practice, a special permit is required and the drug must be used in a controlled research setting as part of a clinical trial, which seems to be a reasonable way to open the doors to research on cannabinoid compounds while still limiting the potential for abuse.


In my laboratory, we have been actively investigating what the best targets for treating neuropathic pain might be and how THC could be safely and effectively delivered to those targets. 

There are a number of challenges in using THC therapeutically. Smoking marijuana or consuming THC in edible form is impractical for the treatment of ocular disease; these systemic applications deliver an unpredictable dose with unwanted systemic side effects.


Sublingual and dermal administration have similar effects and are probably not appropriate for ocular conditions. For these reasons, and due to a lack of evidence of predictable, long-lasting therapeutic effect, a number of professional organisations, including the Canadian Ophthalmological Society and the American Academy of Ophthalmology, have taken positions against the use of systemic THC treatment for ocular conditions.


Local application of THC is considerably more compelling. Cannabinoid eye drops have been investigated and are available for glaucoma from at least one small manufacturer. But noone yet has been particularly successful with this approach due to the challenges of formulating the drops appropriately.


THC and most other pain-relieving or anaesthetic compounds are quite lipophilic. Like oil with water, they do not mix well with the aqueous solutions in most eye drops, making it difficult to get THC into the target ocular tissues.

Enhanced topical drug delivery


Recently, we have been investigating the use of a novel semi-fluorinated alkane (SFA) drug delivery technology (EyeSol, Novaliq) as a vehicle to deliver cannabinoids to the ocular surface. This class of molecules has a number of advantages as an eye drop.


EyeSol-based drops contain no water, so they mix well with lipophilic substances, including cyclosporine and THC, and allow them to remain solubilised instead of separating out in the bottle. They have a very low surface tension so a drop on the eye rapidly forms a very thin layer, giving it spreading properties that are far superior to an aqueous eye drop (Figure 1).


These properties should help to distribute a drug across the uneven ocular surface without the drug being immediately drained or spilling out of the eye as excess aqueous. SFA molecules are metabolically inert and do not interact with the immune system. Finally, they have a refractive index similar to water, so they do not disturb vision the way oil emulsions of lipophilic ingredients can.


In several observational trials we conducted, q.i.d. treatment with an EyeSol delivery vehicle alone resulted in a highly significant reduction in corneal staining and a 20-point improvement in OSDI scores after just six weeks.6 We thought that if this vehicle could be combined with a compound like THC for pain and inflammation, it could be very beneficial in dry eye treatment.


We began to conduct experiments using an established mouse model for dry eye disease that relies on behavioural testing methods to determine pain levels, as well as other testing methods (Figure 2). We compared a group treated with EyeSol THC eye drops to a control group treated with topical cyclosporine.


One-year results of these preclinical studies suggest that the drop is at least as effective as cyclosporine and may have dual or even triple mechanisms of action, including lubrication, anti-inflammation and pain reduction. Although we continue to evaluate various parameters, the pharmacodynamics thus far are very promising.


We are fairly confident that topical application of THC dissolved in EyeSol will not result in any measurable systemic effects. The first human clinical trials in dry eye disorder are expected to begin in the second half of 2018.

Understanding neuropathic pain


Even as research into THC delivery to the ocular surface continues, we have also been seeking to gain a better understanding of neuropathic pain and the characteristics of patients who may suffer from this form of dry eye. To do this, we in the dry eye clinic have been working closely with experts from the University of Cologne’s pain clinic.


We retrospectively evaluated 52 patients seen in our dry eye clinic who fell into the ‘pain without stain’ category. These subjects had normal Schirmer’s, no corneal staining and no signs of blepharitis, but they had OSDI scores >40, in the ‘severe’ symptom range (median score 77).


In addition to a very thorough history and examination in our clinic, many of the patients also underwent a full pain inventory and Hospital Anxiety and Depression Score (HADS) questionnaire. Comorbidities included depression (n=9), chronic pain syndrome (9), anxiety disorders (4), and prior eye surgery (17).7 Other researchers have also recently shown that severe dry eye pain is correlated with antidepressant use but not with corneal staining.8


For ophthalmologists, these are exactly the sort of patients who are mystifying at best, and often get dismissed as people whose symptoms are “just” psychological. To the pain experts we consulted, however, it was very clear that these were typical pain patients, with the same types of concomitant psychosomatic conditions they often see among patients who suffer from chronic headache or back pain.


A typical patient in our study, for example, might have fibromyalgia and rheumatoid arthritis, with an OSDI score of 65 but no clinical signs of dry eye. Upon questioning, she might have first noticed the dry eye pain following LASIK or around the time of a particularly stressful life event, such as the death of a close family member.


In some cases, the patients had no response to topical anaesthesia or to systemic pain medications, which was quite interesting, since it indicates there is something very unusual going on with regards to their pain response. It seems that these individuals may be predisposed to systemic neuropathic pain, of which ocular pain is but one manifestation.


These insights have changed the way I practice in a number of ways. For example, I have started using the HADS questionnaire more frequently for patients with severe symptoms. I ask broader questions about fatigue, anxiety and depression as part of my history taking.


Recognising that ocular surgery can trigger an underlying pain syndrome, I am more thoughtful about evaluating postoperative patients with unexplained symptoms to determine whether they might be most appropriately managed as a pain patient. As medical doctors, it is our responsibility to see the whole patient and, when appropriate, help them to seek treatment for systemic autoimmune disorders, psychosomatic illnesses and other pain syndromes.

Research implications


‘Pain without stain’ patients provide us with a model to understand the process of neuropathic dry eye. Because they do not have significant meibomian gland dysfunction or aqueous deficiency, we are able to isolate the neuropathic disease and hopefully identify new therapies to relieve their symptoms.


While these patients represent what is probably a very rare subtype of dry eye, it is likely that many more dry eye patients who do have clinical signs also have neuropathic pain as a component of their dry eye. In fact, I believe that most of the patients who fail, even partially, to respond to stepwise, appropriate dry eye therapy or for whom resolution of signs does not lead to significant improvement in symptoms, might also have an additional neuropathic disorder.


What we learn from treating the extreme form, therefore, has the potential to benefit a much broader range of patients whose pain is inadequately addressed with current therapy.


It has become clear to me that there is a strong unmet need for treatments that specifically address ocular surface pain. Although much research remains to be undertaken, I am optimistic about the potential for cannabinoid therapies, particularly if we are able to confirm that use of an SFA drug delivery technology is effective in reaching the target tissues without systemic side effects.

References


Rosenthal P, Baran I, Jacobs DS. Corneal pain without stain: Is it real? Ocul Surf. 2009;7(1):28-40.


Rosenthal P, Borsook D. Ocular neuropathic pain. Br J Ophthalmol. 2016;100(1):128-134.


Nelson JD, Craig JP, Akpek EK, et al. TFOS DEWS II introduction. Ocul Surf. 2017;15:269-275.


Belmonte C, Nichols JJ, Cox SM, et al. TFOS DEWS II pain and sensation report. Ocul Surf. 2017;15(3):404-437.


Toguri JT, Caldwell M, Kelly MEM. Turning down the thermostat: modulating the endocannabinoid system in ocular inflammation and pain. Front Pharmacol. 2016;7:304.


Steven P, Scherer D, Krösser S, et al. Semifluorinated alkane eye drops for treatment of dry eye disease—a prospective, multicenter noninterventional study. J Ocul Pharmacol. Ther 2015;31(8):498-503.


Steven P, Schneider T, Ramesh I, et al. Pain in dry eye patients without corresponding clinical signs—a retrospective analysis. Association for Research in Vision and Ophthalmology. 2016, Abstract 2848-A0057.


Satitpitakul V, Kheirkhah A, Cmej A, et al. Determinants of ocular pain severity in patients with dry eye disease. Am J Ophthalmol. 2017;179:198-204.



Professor Philipp Steven, MD


E: [email protected]


Prof. Steven is principle investigator for the Ocular Surface Group in the Department of Ophthalmology at the University of Cologne, in Germany. He consults for and receives research funding from Novaliq and has a patent pending related to the work described within this article.


VIDEO: Consider neuropathic pain in stubborn dry eye

Posted by australiandryeye on November 2, 2017 at 6:20 PM Comments comments (0)

CHICAGO – Rich Mangan, OD, and Scott Hauswirth, OD, discussed a new area of ocular surface disease involving chronic, or neuropathic, pain.


Hauswirth said to consider this condition in dry eye patients who experience light sensitivity and those with symptoms that tend to never go away despite treatment.


https://www.healio.com/optometry/cornea-external-disease/news/online/%7B38eae214-7dac-483f-b33c-095b0c4f398d%7D/video-consider-neuropathic-pain-in-stubborn-dry-eye" target="_blank" rel="nofollow">Video Link


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