In-depth Insights into Stem Cells and Fungal Keratitis on Day 1
Hold onto your hats and water your horses: The 7th Asia Cornea Society (ACS 2020) Biennial Scientific Meeting is happening now!
The online meeting, originally slated to be held in Osaka, Japan last December, has shifted online thanks to COVID-19 (like most scientific events right now) — but the meeting still has all the highlights, including the latest data, study results and surgical techniques from world renowned ophthalmologists.
The meeting kicked off with ACS 2020 Congress President Professor Kohji Nishida, who delivered the opening remarks and thanked organizers and attendees.
ACS Congress President Professor Donald Tan spoke next. He noted that this year represents a landmark for the Asia Cornea Society: “It’s grown from a fledgling society established in 2007 with seven countries and seven council members, to an international cornea society which hosts one of the most popular and successful international cornea meetings globally.”
Prof. Tan also made the important announcement that current Vice President Dr. Shigeru Kinoshita will become the next ACS Congress president.
So, without further ado … check out the highlights from Day 1 in this special issue of CAKE Today.
Yeehaw, it’s the opening ceremony!
One key announcement was the signed memorandum of understanding (MOU) between the ACS and the Japanese Cornea Society (JCS). This strategic partnership will help further education and development in the future as Japanese cornea societies have played a key role in the establishment of ACS over the years, said Prof. Tan. He added that this is especially fortuitous now, as the new ACS president is Japanese.
“The Japan Cornea Society has tried to promote globalization. This signing of the MOU is truly one of the biggest events in the history of the JCS,” shared Prof. Yuichi Hori, JCS president.
The newly formed Indonesia Cornea Society (INACORS) was up next for their MOU with ACS. Dr. Johan Hutauruk, INACORS president, reiterated his hope for continued strengthening of relationships and collaboration between the societies.
Awards were next on the agenda. For his vast contributions to cornea regeneration and stem cells, Prof. Kohji Nishida was the recipient of the Asia Cornea Foundation Lecture. The prestigious Asia Cornea Foundation Medalist winner was announced next and went to Prof. Friedrich Kruse, while the Association of Eye Banks of Asia (AEBA) Award was presented to Prof. Naoshi Shinozaki. The accolades concluded with Dr. Yuichi Ohashi, who received the Saiichi Mishima Award.
Finding the right niche…
Although stem cells have been in our vocabulary for quite some time, their use in medicine is still in development. As such, ACF Medalist Prof. Friedrich E. Kruse from Germany delivered his award-winning lecture on Principles of Niche Regulation for Improved Therapy of Limbal Stem Cell Disorders.
He began with an image of the eye, pointing to the Palisades of Vogt — this is where it’s believed stem cells reside. Prof. Kruse then shared a study created by a research team including prominent ACS members. It defined limbal stem cell deficiency (LSCD) as “an ocular surface disease caused by decrease in the population and/or function of corneal epithelial stem/progenitor cells that leads to the inability to sustain normal homeostasis of the corneal epithelium.”
There are multiple conditions that can result in a stem cell deficiency and lead to LSCD, he shared. This includes multiple ocular surgery, long-term contact lens wear and chemical burns, just to name a few. These can cause conjunctivalization, where the conjunctiva grows over the cornea, the presence of a hazy epithelium, plus others. “Consequently, most patients suffer from pain and decreased vision,” he explained.
A couple years following this study, researchers (including some ACS members) published information on management and therapy for LCSD, which provides an overview of surgical treatment. In unilateral or bilateral stage I and IIA of the disease, Prof. Kruse said that observation, medical treatment or removal of the diseased tissue might be sufficient. On the other hand, for unilateral or bilateral LSCD stages IIB and III, medical treatment is not sufficient. “We have to rely on auto limbal stem cell (LSC) transplantation or allo LSC transplantation,” explained Prof. Kruse, adding that there are also other measures.
Prof. Kruse then provided a detailed deep dive into the considerations still required, as well as future approaches. One study focus is on limbal melanocytes, which are vital components of the corneal epithelial stem cell niche. They not only provide protection from UV light and oxidative stress, they also suppress the LEPC (limbal epithelial progenitor cell) differentiation and may contribute to the maintenance of the progenitor prototype, he continued.
“They are involved in immune regulation and might be important for the formation of the vascular integrity of the limbal barrier,” said Prof. Kruse. “Based on their powerful regulatory, immunosuppressive and anti-angiogenic properties, limbal melanocytes have great potential for LEPC ex-vivo expansion and therapeutic application.”
Furthering the stem cell frontier
Next was another important talk: the ACF Lecture by Prof. Kohji Nishida from Japan on Development of Stem cell-based Therapy for Limbal Stem Cell Deficiency. Prof. Nishida began by sharing his interest in stem cell therapy, which was sparked by a paper from the late 1980s.
“In clinical practice, it’s important to evaluate limbal stem cell function,” said Prof. Nishida, who then covered three diagnostic markers for the loss of corneal epithelial stem cells. On slit lamp examination, these include: the disappearance of the Palisades of Vogt, a superficial invasion of blood vessels, and conjunctival epithelial invasion into the cornea.
Prof. Nishida continued that there are pros and cons for surgical management of complete LSCD; the current standard of care is allogeneic-limbal transplantation with amniotic membrane transplantation. However, he shared a study that showed long-term outcomes for severe LSCD were poor due to a high incidence of immune rejection. This has led to the development of cultivated corneal epithelial cell sheet transplantation (CLET) to reduce the risk of rejection, as well as other procedures including: autologous cultivated oral mucosal epithelial cell sheet transplantation (COMET), which has been found to be promising for the treatment of bilateral LSCD, but problems still remain.
“We are currently investigating the use of iPS (induced pluripotent stem cells) cell-derived corneal epithelial cell sheets fabricated from iPS cells developed for clinical use and the first-in-human clinical trial is now ongoing,” concluded Prof. Nishida.
Takeaways in fungal keratitis management
Another highlight on Day 1 was a plenary lecture on Perspectives Learned in the Diagnosis and Management of Fungal Keratitis from Dr. Venkatesh N. Prajna of India. He presented several methods he’s focusing on to enhance microbial diagnosis. One included an interesting study he co-authored that explored the use of fluorescent smart probes (which are normally used to image and diagnose bacteria or other issues in the lungs) for the rapid detection of microbial isolates that cause corneal ulcers.
“We found that the smart probes were reasonably accurate to pick up gram positive and gram negative bacteria and fungi with equal or higher specificity — and that is the important thing,” said Dr. Prajna. “If we are able to develop low-cost fluorescent microscopes, then we have a scope for doing a point-of-care clinical application to aid in the diagnosis of microbial keratitis.”
Another topic he discussed was metagenomics, which he said could improve diagnostic accuracy and sensitivity — but the problem is the so-called experimental noise associated with this technology, he explained. “We feel this is an exciting tool but right now, it requires a sophisticated lab with trained technicians, but if we are able to master it somehow, then the chance of bringing the cost down becomes easier.”
Regarding management of microbial keratitis, he focused on antifungal medications and collagen cross-linking. For antifungals, he presented results from the MUTT I study that found natamycin performs better than voriconazole, which is contrary to what was previously thought, he shared. “And natamycin is much, much better when you are dealing with Fusarium patients … what is interesting is that different fungi respond differently to different antifungals.”
He then pivoted to a study comparing cross-linking with medical therapies. They found that cross-linking is not particularly useful in reducing positive cultures in fungal keratitis. “And in fact, cross-linking causes a decrease in visual acuity (VA),” he added. Further, a follow-up study at one year confirmed that cross-linking had a negative impact on VA.
Dr. Prajna says he’s learned several lessons over his 20-odd years of research into fungal keratitis. In his final comments, he reiterated that even within the same species, there can be considerable variation in fungi. In addition, killing the agent alone does not necessarily mean the disease is controlled.
“The last part is the most interesting thing that I’ve learned: We need to supplement our anti-infective medications with something that is topical and selectively immunosuppressant based on the host response; this, along with the use of anti-infectives, is the way to go,” concluded Dr. Prajna.
Editor’s Note: The Asia Cornea Society (ACS) 2020 Biennial Scientific Meeting took place online from April 28-29, 2021. Reporting for this story also took place during the virtual meeting.
