As the world's first irreversible blinding disease, glaucoma is not far away from us.
At present, the spectrum of the main blinding eye diseases in mainland China has changed from trachoma and cataracts in the past to age-related and metabolic-related eye diseases such as glaucoma and fundus disease.
A more direct data corroboration is that the "China Glaucoma Guidelines (2020)" issued by the Chinese Medical Association Ophthalmology Society shows that there are more than 20 million glaucoma patients in the mainland at this stage, of which more than 1/4 of the patients are going blind.
Despite such a large patient size, humans have not found a cure to completely defeat glaucoma. Although the road ahead is long, researchers and entrepreneurs continue to follow this problem and gradually bring new hope to patients.
Coinciding with World Glaucoma Day, Arterial Network will start from the aspects of diagnosis, clinical treatment and medication, sort out the current situation and characteristics of the development of the glaucoma market, and look forward to its future direction.
Glaucoma diagnosis and treatment map (partial)
diagnosis:
Insufficient resources, cognitive loss
At this stage, the dilemma faced by glaucoma patients is not only that there is no complete cure, but also that there are challenges in the screening stage.
Since glaucoma is an irreversible damage to the optic nerve caused by high intraocular pressure, it cannot be irreversible once blind. Therefore, in the consensus on the diagnosis and treatment of glaucoma, there has always been an emphasis on early detection, early diagnosis and early treatment.
However, the reality is that the diagnostic coverage rate of mainland glaucoma is still at a low level, 90% to 95% of open-angle glaucoma, more than 60% of closed-angle glaucoma have not been diagnosed in time, while the diagnostic coverage rate of developed glaucoma is mostly 30%-50%.
Behind this situation, on the one hand, it is due to the lack of public awareness and attention to glaucoma, on the other hand, it is limited by the lack of medical resources and the limitation of screening work.
Similar to most chronic diseases, most patients do not directly perceive eye discomfort in the early stages of glaucoma. Glaucoma, which is in the acute attack period, in addition to eye discomfort, is often accompanied by symptoms such as headache and nausea, so it is easy to be ignored by patients.
Looking at the specific screening links later, at this stage, there are only less than 50,000 ophthalmologists in the mainland, and if the screening of the whole population is to be realized, the cost is bound to be huge. Moreover, the projects involved in glaucoma screening, such as fundus examination, intraocular pressure measurement, and atrial corner examination, are mainly concentrated in the hospital scene, which further reduces the frequency of patients' active screening behavior.
Therefore, how to popularize the early screening and early diagnosis of glaucoma in an effective way, under the premise of reducing medical costs and improving the convenience of services, has become a topic discussed by many researchers and innovators.
AI technology empowerment
In recent years, the progress of AI technology has ushered in innovative development in the diagnosis and treatment of many diseases, among which AI-assisted medical image interpretation and diagnosis have also made substantial progress. And the support of AI technology also provides a new opportunity for the early screening and popularization of glaucoma.
Theoretically, the diagnosis and treatment of glaucoma often involves visual field monitoring, fundus optic nerve examination and other items, which can also be used as an entry point for combining AI.
Although the use of AI to achieve early screening and diagnosis of glaucoma is a little slower than other ophthalmic AI products, such as sugar mesh screening systems, it is also steadily advancing.
In June 2020, the "Guidelines for the Standardized Design and Application of Artificial Intelligence Glaucoma Auxiliary Screening System Based on Fundus Photography" organized by the Glaucoma Group of the Ophthalmology Branch of the Chinese Medical Association was officially released, which effectively standardized the design and clinical application of the AI glaucoma auxiliary screening system.
It is understood that the "artificial intelligence glaucoma screening system" developed by Tencent Miying can realize the auxiliary diagnosis of early glaucoma, which can be identified before the patient's vision is impaired, so that glaucoma patients can get more timely and effective treatment, and the accuracy rate exceeds 95%.
In addition, enterprises such as Eagle Pupil Technology and Zhiyuan Huitu have also developed AI products suitable for glaucoma screening, which can not only provide more feasible paths for the prevention and treatment of glaucoma screening in the mainland, but also effectively alleviate the screening dilemma caused by insufficient medical resources.
Home testing of the blue ocean market
In addition to insufficient medical resources, another dilemma of glaucoma screening is the inefficient traditional testing methods. Under normal circumstances, glaucoma screening requires comprehensive inspection of multiple indicators such as intraocular pressure, room angle, visual field, and visual disk, most of which need to be equipped with professional equipment and corresponding technical personnel, and the detection time is also long.
Obviously, portable glaucoma screening devices that are lightweight, have short detection times, and are not limited by the environment can obviously be favored by the market. In addition, in addition to the portable attributes, intelligence is also the direction that many companies will consider when developing such products. The integration of intelligent diagnostic technology makes such products, in addition to early screening, also be applied to prognosis course monitoring, providing support for the formulation of disease management programs.
However, at this stage, most portable glaucoma detection products are mainly through the detection of a single indicator (such as intraocular pressure, visual field) to achieve auxiliary screening of glaucoma, clinically the diagnosis of glaucoma still needs to combine multiple index parameters. However, from a disease management perspective, such products can also provide great value for screening and prognosis of patients with glaucoma.
Drug therapy: prostacyst drugs are the mainstay,
New treatments are constantly in the pipeline
Let's look at the treatment of glaucoma.
At this stage, in the treatment of glaucoma, the intraocular pressure of patients is mainly controlled by reducing intraocular pressure, and commonly used strategies are drugs, surgery and laser treatment. In general, drugs are mostly used in the early stage of glaucoma, and in the later stages, intraocular pressure is controlled by surgical means, so drug treatment is also the first choice for glaucoma treatment.
According to the drug data of urban public hospitals in 2020, the sales generated by anti-glaucoma preparations and mydriatic drugs reached 569 million yuan, and it has maintained a high level in the field of ophthalmic drugs in the past 6 years.
Specific to the type of drug, starting from the intraocular waterproofing generation and outflow pathway, the mechanism of action of intraocular pressure-lowering drugs mainly has the following three types: reducing aqueous humor generation, promoting the outflow of aqueous humor through the trabecular network pathway, and promoting the outflow of aqueous humor through the uveal sclera pathway.
In addition to the above drugs, hypertonic dehydrating agents can also achieve the effect of reducing intraocular pressure by increasing the plasma osmolality in a short period of time and dehydrating the eye tissue.
Ideally, glaucoma treatment drugs should have the characteristics of the largest single-drug intraocular pressure reduction effect, no obvious side effects, no rapid drug resistance, and long-term control of intraocular pressure fluctuations. Prostaglandin derivative drugs have the above characteristics, but also by the major guidelines unanimously recommended as open-angle glaucoma first-line drugs, urban public hospitals also show that the sales of such drugs account for almost half of the entire anti-glaucoma drugs.
However, it should be noted that at this stage, in the actual clinical use of prostaglandin derivative drugs, there will still be conjunctival congestion, eyelash growth and other side effects, which will affect the patient's medication compliance. Therefore, at this stage, the glaucoma drug treatment market is still a field where the demand is far from being met, but the industry has never stopped exploring better therapies.
For example, the ROCKLATAN, developed by Aerie Pharmaceuticals approved by the FDA in 2019, is based on the combination of Rhopressa and the widely used latanoprost, which has a more significant intraocular pressure reduction effect and fewer side effects than a single drug.
Unlike most companies, Alnylam chose to develop RNAi therapy for glaucoma. It is understood that Alnylam is currently working with regenerators to develop an RNAi therapy for the treatment of glaucoma, in which a single intravitreal injection in a mouse model can reduce intraocular pressure by more than 5 months.
In addition, similar to most fields, eye medication also faces the problem of drug delivery. The eye is a relatively independent organ, and the presence of its blood-eye barrier greatly reduces the bioavailability of the drug in the eye.
Therefore, the design of new dosage forms for ocular sustained release administration and the prolongation of the ocular retention time of the drug have also become an important direction of current ophthalmic drug research.
It is understood that as early as 2020, Allerga's biodegradable bemeprost sustained-release implant Durysta successfully obtained FDA approval, becoming the first anterior chamber, biodegradable, sustained release implant.
In China, some innovative enterprises are also trying to solve the problem of eye medication barrier through the combination of medicine and equipment, and with the cooperation of implanted devices, the therapy can play a better effect than a single drug.
Surgical treatment:
Minimally invasive techniques are gradually emerging
In general, when glaucoma develops to the mid to late stages, it requires intervention through surgical treatment.
At this stage, the commonly used clinical glaucoma surgery mainly includes traditional filtered anti-glaucoma surgery (trabeculectomy, non-penetrating trabecular surgery, etc.) and minimally invasive internal drainage surgery based on the aqueous humor outflow pathway or micro-incision anti-glaucoma surgery (trabecular ablation, mucosal tubular plasty, aqueous water outflow pathway reconstruction, etc.).
In order to understand the current innovative direction in the surgical treatment of glaucoma, Arterial Network has sorted out some of the capital events that have occurred in the field of glaucoma surgery in the past three years.
As can be seen from the above figure, the research and development of innovative solutions related to minimally invasive glaucoma surgery (MIGS) is currently a market entry point that is more concerned.
In fact, in the clinic, minimally invasive glaucoma surgery is also a surgical method that has attracted widespread attention in recent years, which is characterized by small internal incisions, high safety, and existing research evidence shows that the complications caused by minimally invasive glaucoma surgery are significantly lower than traditional trabeculectomy.
However, although the clinical development of glaucoma is becoming more and more recognized at this stage, there are still obvious gaps in domestic minimally invasive glaucoma surgery products, and no domestic products have been officially approved for listing.
In terms of imported products, in April 2019, the glaucoma drainage tube Zanyi (XEN) developed by Allergan was used for the first time in Hainan Boao Super Hospital. Subsequently, in March last year, XEN officially obtained NMPA certification, which is also the first medical device product approved for marketing through domestic real-world data.
Also in Boao Lecheng, Hainan, in January last year, the glaucoma drain preserFLO developed by Santian Company successfully carried out the first implant surgery in China at the Hainan Boao Super Hospital. In fact, the product has already obtained CE certification in 2012 and has been listed in Europe for many years, and its effect and safety have been fully clinically verified.
In China, although there are no domestic glaucoma minimally invasive surgical products on the market, this does not mean that domestic companies have no breakthroughs in this regard.
It is understood that Hessgaide, which completed angel rounds and pre-A rounds of financing last year, is an innovative company focusing on minimally invasive solutions in the field of glaucoma, and the peripheral diameter of the implanted stent MicroCOGO developed by it is smaller than most similar products. It can be seen that in terms of the manufacturing capacity of ultra-micro and fine devices, the performance of domestic enterprises is not inferior.
Founded in 2020, Wenzhou Xiaoliang Medical Technology Co., Ltd. is also focusing on the research and development of minimally invasive treatment solutions and products for glaucoma, and its glaucoma stent products under research have excellent performance in the scope of adaptation, which can greatly improve the success rate of surgery. With the innovative nature of the solution, Xiaoliang Medical also successfully completed its first round of financing last year.
Write at the end
At this stage, in addition to surgical treatment, laser treatment is also a common strategy for the treatment of glaucoma. In this field, there are also many innovators, such as BELKIN Laser DSLT (Direct SLT), a one-second fully automatic glaucoma laser treatment device developed by BELKIN Laser, which can be treated at the push of a button.
However, so far, for glaucoma, we still can't talk about "cure", and the existing multiple means can only be early detection and delay the onset of the disease.
But with advances in technology and medicine, many diseases that used to be called incurable diseases have been cured. The emerging innovative technologies and therapies are also constantly changing the diagnosis and treatment of this disease of glaucoma, and more and more innovators are also choosing to move forward in this field.
We also expect that in the future, there will be more prescriptions for patients, and glaucoma will no longer steal our vision. Our light can truly be in our own hands.
*Cover image source: 123rf