A doctoral student finds a flaw in a method long used to diagnose astigmatism and comes up with a solution: the Cassini. This diagnostic tool provides images of both the front and back surfaces of the cornea for a more accurate picture to guide medical procedures. Eyes diagnosed with astigmatism essentially have a refractive error, or problems focusing light. Thus, instead of having a single focus, light on the front or back (or both) of the retina focuses on multiple points.
A procedure to test the eye for astigmatism is called retinoscopy, or by shining a light into the eye while manually introducing a series of lenses between the light and the eye. To give a proper diagnosis of the cornea, a clinician must be able to understand the cornea’s shape and optical performance; this is done through a process called corneal topography.
In the early 17th century, the earliest corneal topography was done using the reflection of marbles from the cornea. The current Placido-based topography came in the 19th century and used the same principle by assessing the reflection of circular mires or rings—called Placido’s disc or keratoscope—from the front surface of the cornea.
Named after its inventor, Antonio Placido, Placido’s disc is made up of equally spaced alternating black and white rings with a hole in the centre to observe the patient’s cornea. That opening in the middle of the concentric circles houses a convex lens for magnification to aid the examiner.
Corneal topography analysis is commonly used in planning procedures to correct astigmatism, fit contact lenses, and enable the screening of candidates for refractive surgery. In post-operative
situations, corneal topography can help evaluate the dioptric change created at the cornea. The dioptre measures the power of the lens needed to correct vision to normal.
Corneal topography, however, is limited to the central portion of the anterior corneal surface. The need to study not only the anterior but also the posterior and the peripheral parts of the cornea has given way to the creation of new devices that can provide faster and more accurate diagnosis. It is in this landscape that the Cassini was born.
Cassini
The Cassini is a diagnostic device that offers ‘true corneal shape analysis’ for better outcomes in diagnosis and corrective procedures such as refractive surgery, cataract surgery, and corneal transplant. It is also used in examinations like pupillometry and color photography.
One of the inventors, Dr. Arni Sicam, was a Filipino studying for his doctorate at the VU University Medical Center Amsterdam (VUmc) in The Netherlands in 2002 when he started work on the
Cassini. The medical physicist said it was not his purpose to invent anything, and that as a student, he was simply improving on the current method used in ophthalmology for corneal analysis.
He, however, found a flaw in the technique: the Placido rings appear as equally spaced symmetric reflections if the eye is perfectly spherical, and take an oval shape or become distorted if the cornea is irregularly shaped or deformed. Thus, if the patient has astigmatism, the Placido disc becomes less accurate as a diagnostic tool because the process assumes that the cornea is symmetrical.
Sicam set out to find a solution for this inaccuracy. The VUmc Department of Physical-Medical Technology (FMT) provided him with the laboratories and other assistance needed to develop what would become the Cassini technology.
Points system
Instead of rings, the Cassini uses points–red, green, and yellow LEDs–positioned in a unique relationship to four of its neighbours. ‘The advantage of this is you can use the points to be the three-dimensional marker in the cornea, like a GPS system. Also, any irregularity can be picked up,’ Sicam explains.
Aside from providing a better understanding of the corneal surface, the Cassini also enabled the maging and measurement of the back surface of the cornea, which the Placido disc cannot do. Sicam says the points system of the Cassini provides a second reflection—a faint but detectable image of the corneal back surface, which provides the clinician more accurate information on the cornea’s refraction. ‘Without [seeing] the back surface of the cornea, errors in cataract surgery might happen, and the error margin is a difference of about 1 dioptre.
In the spotlight: Shedding light on the cornea
The cornea is the clear, transparent, domeshaped surface that covers the front of the eye. As simple as it looks, it is formed by a highly organized group of cells and proteins. It has no
blood vessels which may nourish it or protect it against infection. This is because the presence of blood vessels may cloud the cornea and prevent it from doing its main function of refracting, or bending light.
As the cornea is responsible for focusing most of the light that enters the eye, it must be free of any opacity to help the eye see better. The cornea acts like a window that focuses light entering the eye, contributing to 65% to 75% of the eye’s total focusing power.
The cornea is made up of five layers: the epithelium, Bowman’s Layer, stroma, Descemet’s membrane, and endothelium. In 2013, it was announced that the sixth layer of the human cornea was discovered by Professor Harminder Dua of the University of Nottingham. The new 15-micron-thick layer—now called Dua’s layer—was found between the stroma and Descemet’s membrane, and is now the fourth of six layers.
That spells the difference between needing glasses and not needing it. If you have the back surface of the cornea, you reduce that uncertainty, and there’s a higher chance that the surgery will successful,’ Sicam says. The Cassini has brought changes to ophthalmology, particularly benefitting patients requiring eye treatment. Before the Cassini, people aimed to be able to wear eyeglasses following cataract surgery. With Cassini, Sicam says, cataract surgeries are conducted with a higher success rate.
‘One of the things happening now is that the demand of patients towards accuracy is higher. Before, people were happy with diagnosis that is not optimal. Now, usually when people go for cataract surgery, they want to come out with no glasses,’ said Sicam.
From laboratory to market
Following the initial technology development of the Cassini at the FMT, Bart Klijsen, Senior Technology Transfer Manager at IXA VU-VUmc (former Technology Transfer Office VU & VUmc) was approached in 2007 by the inventors to assess the potential and feasibility of patenting their new technology. The outcomes of the evaluation process were positive, and a patent was filed. Around the same time, contacts were established with i-Optics to probe the company’s interest in the technology.
i-Optics develops smart tools for eye diagnosis to enable better care for patients, while at the same time increasing efficiency and decreasing costs. The company’s interest was clearly there, and as a first step, VUmc and i-Optics engaged in research collaboration. The collaboration resulted in a second successful joint patent filing, with IXA again in a coordinating role.
‘While discussing the terms of the commercial licensing agreement between VUmc and i-Optics on the two patents, we had to balance two interests: first, to estimate a realistic commercial value of the contribution of the patents to the end product; second, to enable successful valorization of the technology by creating an optimal starting position for i-Optics,’ Klijsen says. Sicam later moved to i-Optics, which provided the company with an inhouse expert on the licensed technology. In the end, it all worked out to the satisfaction of both parties: VUmc managed to find a good home for its technology, and i-Optics created a truly innovative and commercially successful product.
Thomas van Elzakker, i-Optics’ Chief Operating Officer, says i-Optics has been working with universities for the development of products since the company started. The Cassini had been an
obvious choice to license from the VUmc.
‘We saw the potential of what it did. It is not only a machine for the highly accurate measurement of the front of the cornea, but it can also provide an image of the back surface of the cornea. That is rather unique. We know the challenges in that space. We understand the opportunity in serving that need,’says van Elzakker.
With the Cassini, van Elzakker says, the science-tobusiness collaboration had been smooth because each side had distinct roles in steering the Cassini technology from the realm of science to the market. i-Optics was responsible for the further development and commercial rollout of the Cassini, and interested in the opportunity to develop more applications for the product moving forward. On the other hand, VUmc and the inventors are responsible for the academic research and supportive in the valorization of the Cassini technology. ‘We are all happy to license the product. Our goals in that respect are aligned,’ says van Elzakker.
Next frontier
i-Optics counts the United States as its biggest market for the Cassini since it was introduced in 2013. The United States, van Elzakker says, is amarket that is more adventurous when it comes to new technology.
The market entry strategy of i-Optics is to sell the product to well-respected doctors whose stature allows them to immediately try new technology. Cassini is also now beginning to get market traction in Germany, Spain, France, Switzerland, and the Scandinavian countries.
Sicam says that the next frontier for the Cassini is integration. i-Optics has connected the Cassini to the surgical suite of instruments that perform cataract surgery such as the LENSAR Laser System with Streamline.
The Cassini now automatically and wirelessly transfers pre-operative data to the LENSAR, providing ophthalmologists the specific treatment parameters to guide them in decision-making during
surgery.
‘The Cassini measures the shape change in the cornea, so you will get information on what the effect of that incision will be, and that can be recorded. Next time, you can consider that effect. Then you can close the loop because the Cassini also does post-operative measurements,’ says Sicam. i-Optics is also gathering clinical data for presentations and scientific exhibitions to be able to share with more people more information on the Cassini’s performance.
‘We need to do this scientifically. The current customers understand the performance of the Cassini based on its technology, but the next tier [of customers] demand to have clinical proof of what it can do for them,’ van Elzakker says.