What's in the pipeline?
Research, development, innovation and the quest for excellence go hand in hand with the evolution of the ophthalmology industry. With the new wave of phakic IOLs entering the market, each with its own unique offering and capabilities, it's hard to know which lenses will suit you and your patient best. Furthermore, does the introduction of these new refractive correctors threaten the position of the lasers that we have all come to grow to love? It seems that the laser refractive surgery industry is still going from strength to strength. With the advent of new and improved laser systems, which not only carry with them enhanced imaging and diagnostic platforms, but the technological advances in laser development has created systems that provide better refractive outcomes and improved safety and efficiency. Even though surgeons across Europe are slowly adopting the use of phakic IOLs in their practice, there certainly remains a place for laser systems in the refractive surgery market mix.
On a separate note, you may have noticed that we have been paying particular attention to research and development in age-related macular degeneration (AMD) over recent months. I certainly do not feel that this topic can be exhausted at present. This is a disease that blinds millions of people each year, which, in the past, could only be treated by surgical intervention. Naturally, the fact that new, promising therapies are hitting our clinics is causing much excitement, as well as some controversy, amongst the AMD specialist community. The fact that a doctor will soon have an array of therapeutic options available to them for their AMD patients surely justifies this excitement.
Meanwhile, ocular implants as therapies, diagnostics and, surprisingly, as vision restoratives in blind patients, is the new craze in certain ophthalmic applications. Whether those that are currently in development will succeed in trials and be embraced by the community, remains to be seen, but the theory behind these new devices, as well as results yielded so far, seem promising.
In this section, we have homed in on just some of the therapies, devices and lenses that either are just starting to filter into the market or are still undergoing development. Although it is impossible to highlight advances across all areas of ophthalmology, it is our hope to provide you with a glimpse of what certain developers are up to and in which direction development is moving.
Technolas Zyoptix 100 Hertz excimer laser – new developments ahead!
Developers: Bausch & Lomb
Bausch & Lomb scientists have been working tirelessly over the last few years to address any issues relating to the traditional Zyoptix system and to create, what it believes to be the ultimate wavefront-guided system for refractive correction.
Armed with its secret weapon, Gerhard Youssefi, Bausch & Lomb Director of new technology programmes and an "Einstein" of the optical physics world, the company has created a system that has, thus far, yielded clinical data that, to date, is unmatched by any other laser system available.
Scheduled for launch this summer, Bausch & Lomb will be showcasing the improvements to the new system at this year's ESCRS meeting in London during September.
The Zyoptix system incorporates many new features that, collectively, lead to enhanced predictability, refractive outcomes, speed, simplicity and efficiency.
Here are just some of the things you can expect:
So where to next? According to the company, these improvements are just part of its journey to addressing the market's unmet needs and by no means signifies the end destination. These developments are certainly highly significant, with some of Europe's leading refractive surgeons, during a meeting in Munich at the end of March, agreeing that the improvements to the Zyoptix system have yielded outstanding, and unmatched, refractive outcomes. What will you think of it? Watch this space for further developments.
STAR S4 IR excimer laser system with CustomVue
Developers: Advanced Medical Optics
The system has a number of features that contribute to the delivery of precision custom ablations. Iris registration is a fully automated, non-contact method of alignment for delivering the correct treatment to the corneal site. Variable spot scanning allows various beam sizes from as small as 0.65 mm up to 6.5 mm to be scanned over the treatment area, conserving tissue and optimizing treatment times. Active eye tracking captures all three dimensions of intraoperative eye movement without dilation and automatic centring locates and sets the treatment centre to the centre of the pupil.
Approval of the system was based on clinical studies, which demonstrated, at six months, patients receiving the CustomVue high myopia treatment were corrected to 20/40 or better and 84.3% were corrected to 20/20 or better, without the aid of spectacles or contact lenses.
The new system received CE marking in September 2005.
Developers: Advanced Medical Optics
Tecnis multifocal was developed using wavefront analysis of human corneas and as a result its aspheric surface helps reduce spherical aberrations and improve patient outcomes. With its diffractive optics, the lens divides more than 90% of available light over two discrete focal points, with the focal point difference being 4 D, translating to around 3 D on the spectacle plane. The cap C haptics of the lens allow optimal centration, whilst the sharp optic edge has been designed to act as a PCO preventative. It can be injected through an incision of 2.8 mm and the acrylic material has good biocompatibility.
Developers: Advanced Medical Optics
The IOL is indicated for the visual correction of aphakia in persons 60 years of age or older in whom a cataractous lens has been removed and who may benefit from useful near vision without reading and increased spectacle independence across a range of distances. It is intended to be placed in the capsular bag.
Visian ICL & Visian Toric ICL
Developers: STAAR Surgical
Visian ICL was recently approved by the FDA for use in the correction of myopia in adults and is approved for sale in 41 countries, including the EU. Visian TICL received full CE marking in 2003 and is currently undergoing FDA clinical trials for the treatment of myopic astigmatism.
Developers: Alcon Laboratories
The AcrySof ReSTOR lens uses a combination of three technologies, apodization, diffraction and refraction and can be injected through incisions of 3 to 3.2 mm. It is made from a biocompatible acrylic material that has demonstrated excellent biological performance in the eye. In trials, 84% of subjects demonstrated combined uncorrected vision of 20/25 or better for distance and 20/32 or better for near.
Tek-Clear received the CE Mark approval for the treatment of presbyopia in January of this year. It features a 5.0 mm optic, 360° full bag haptic, square edge design and an anti-glare shield. Customized haptic sizes are available.
MC X11 ASP
Developers: HumanOptics AG
The Crystalens model AT-45 SE accommodating posterior chamber IOL is a modified plate haptic lens with hinges across the plates adjacent to the optic. It is designed to move forward and backwards in the eye like the natural crystalline lens. The lens is a biconvex silicone plate lens with a 4.5 mm optic and it has hinged haptics with two polymide flexible loop extensions on the ends of each plate. The length from plate haptic end to plate haptic end is 10.5 mm. Crystalens is available in the powers +10D to 33D in 0.5D steps and +16D to +27D in 0.25 steps.
Crystalens is approved for the visual correction of aphakia secondary to the removal of a cataractous lens in adult patients with and without presbyopia.
The mechanism of action of this lens is based on a lens complex formed by two optics linked by a spring system that, prior to ocular implantation, are separated by approximately 3.7 mm. When implanted within the capsular bag however, interoptic separation is significantly reduced because of compressive tension exerted by the capsular bag. Characteristic elements incorporated within the lens complex control minimum separation and hence set the resting distance refraction at emmetropia.
Developers: Corneal Laboratoires
Due to its shape, ICARE avoids contact with the cornea, thereby preventing alteration of corneal tissues and the flexibility of the hydrophilic material ensures little pressure is applied on ocular structures and hence the risks related to this type of implant are reduced.
The lens fits into the anterior chamber with a design that adapts to the anterior segment anatomy being parallel to the posterior curvature of the cornea. It is available in powers ranging from -20 D to -5 D. Clinical investigations have proven its stability and refractive performance.
Kelman Duet Implant
This IOL has demonstrated excellent safety and efficacy in multicentre clinical investigations and is only available in Europe.
Although each of the four lenses carries its own unique qualities, one thing that is inherent in each are the features that
make it a LISA lens:
The company's LISA portfolio of lenses includes:
KS-3Ai preloaded aspheric IOL injector
Developers: STAAR Surgical
The lens is preloaded and ready to use, the delivery is controlled and offers a sterile pathway directly to the eye. The disposable injector can be used with one or two hand technique and features a push or screw technology in one system. It is available in 0.5D steps from +12.5D to +28.5D with phaco neutral incision size of 2.8 mm. The KS-3Ai will be launched in Europe in May 2006.
Developers: Novartis Ophthalmics
Visudyne is the first drug therapy to be approved for the treatment of wet age-related macular degeneration (AMD). When activated by light, it causes local damage to the neovascular endothelium in the macula, resulting in vessel occlusion thereby slowing or stopping the progression of AMD.
Visudyne photodynamic therapy is a two-step process requiring administration of both drug and light. First Visudyne is injected intravenously through the arm for 10 minutes and is then "activated" by shining a precalculated dose of light, at a wavelength of 689 nm, for a period of 83 seconds. Therapy can be safely reapplied at three-month intervals.
The benefit of administering Visudyne in combination with steroids and anti-VEGF therapies, in the treatment of AMD, is currently being investigated.
Macugen (pegaptanib sodium)
Developers: OSI Pharmaceuticals/Eyetech/Pfizer
Macugen is an aptamer, a pegylated modified oligonucleotide, which selectively inhibits the vascular endothelial growth factor isoform, VEGF165.
It was approved in the US to treat all subtypes of wet AMD in December 2004, whilst European approval was granted in January 2006, making Macugen the first VEGF inhibitor to be approved for the treatment of all types of wet AMD.
Please go to page 42 for further information on Macugen.
Developers: Novartis Ophthalmics
Lucentis is a humanized monoclonal antibody fragment designed to bind and inhibit VEGF-A, a protein that plays a critical role in angiogenesis. Consequently Lucentis blocks new blood vessel growth and leaks, which lead to wet AMD disease progression and vision loss.
Results from a recent Phase III clinical study of 716 patients with minimally classic or occult wet AMD showed that, at 12 months, approximately 95% of patients treated with Lucentis maintained or improved vision (defined as a loss of less than 15 letters in visual acuity on the ETDRS chart). It was the first time that a treatment for AMD improved vision rather than just slowed the progression of vision loss.
Novartis has now submitted Lucentis for European Union approval.
Retaane (anecortave acetate)
Developers: Alcon Laboratories
Retaane is a broad spectrum angiostatic agent that inhibits angiogenesis irrespective of the initiating angiogenic signal. It is administered as a periocular posterior juxtascleral depot.
A Phase III prospective, masked, randomized, multicentre, parallel group, active control, non-inferiority trial in 530 patients demonstrated good efficacy in the treatment of wet AMD and, on this basis, Alcon submitted a marketing application to the European Medicines Agency in 2004. However, the company withdrew the application earlier this year giving research, development and marketing strategies as reasons for doing so.
Developers: Miravant Medical Technologies
Photrex uses rostaporfin, a light activated drug, to destroy abnormal blood vessels in the eyes of patients with wet AMD.
Following positive results from a Phase III trial, Miravant filed a New Drug Application in March 2004 and announced in September of that year that the US FDA had issued an approvable letter. The letter included a request for a confirmatory clinical trial, which is now underway in the United Kingdom, Central and Eastern Europe.
Developers: Regeneron Pharmaceuticals
The VEGF Trap literally "traps" vascular endothelial growth factor (VEGF), preventing it from stimulating the VEGF receptor and therefore halting the progression of wet AMD.
In preclinical experiments, the VEGF Trap has been shown to prevent the development of abnormal blood vessels in the eyes of animals with conditions resembling AMD. Preclinical studies have shown that the VEGF Trap inhibited the growth of new blood vessels when given intravenously, as well as when administered directly into the eye.
Regeneron is now initiating Phase II trials with the agent.
Evizon (squalamine lactate)
Evizon is a systemically administered, anti-angiogenic drug under development for the treatment of wet AMD. It is a molecule with a multi-faceted mechanism of action that blocks the action of a number of angiogenic growth factors, including VEGF, cytoskeleton and integrin expression.
The results of a Phase II randomized, multicentre, double-masked trial evaluating the safety and efficacy of Evizon were promising. Of 35 subjects receiving a 40 mg dose, 28 recorded stabilized or improved vision (defined as a loss of less than 15 letters in visual acuity).
Genaera is planning to initiate a further Phase II trial exploring the safety and efficacy of Evizon in doses of up to 160 mg.
Developers: Sirna Therapeutics
Sirna-027 is a chemically modified short interfering RNA (siRNA), targeting Vascular Endothelial Growth Factor Receptor-1 (VEGFR-1), designed to shut down activation of angiogenesis initiated by VEGF.
Results from a Phase I, dose escalation trial in 22 patients, showed it to be safe and well tolerated with 100% of patients showing visual acuity stabilization from a single injection after eight weeks of treatment. Furthermore, the agent induced clinically significant improvement in visual acuity in 23% of patients (defined as an improvement of three or more lines). Decreases in central foveal thickness were also apparent in the majority of patients.
Transfer of developmental responsibilities will now pass to Allergan. Both companies anticipate Phase II trials to begin during 2006.
Developers: Acuity Pharmaceuticals
Cand5 works on the basis of RNA interference; turning off VEGF before it is made by destroying the VEGF messenger RNA. By dong this, it prevents new blood vessels from leaking and growing.
A Phase I, open-label, dose escalation study demonstrated Cand5 to be safe and well tolerated and a Phase II trial has now been initiated.
AdPEDF (adenoviral pigment-epithelium derived factor) uses a DNA carrier, adenovector, to deliver human Pigment Epithelium-Derived Factor gene that results in the local production of AdPEDF in the treated eye. AdPEDF is normally produced in the eye and serves the purpose of regulating blood vessel growth and is also a neuroprotective agent of the photoreceptors.
GenVec has completed the dose escalation portion of a Phase I trial in 28 patients with advanced wet AMD. Positive changes in visual acuity and retinal appearance were noted at higher dose levels and no severe adverse drug related events were observed.
GenVec now plans to initiate enrolment in a further Phase I trial.
Electronic chip retinal implant
Developers: retina implant AG
Retina Implant AG has developed an electronic chip that is implanted in the eye under the retina to potentially restore partial vision to blind people.
The first operations were successfully performed in humans at the end of 2005 when two blind patients received the implant. After several weeks of monitoring, the patients were able to correctly identify the location and direction of spots of light and patterns. The trials are being headed by Professor Eberhart Zrenner of the University Eye Hospital Tübingen, Germany and supported by the German Federal Ministry of Education and Research. The implant consists of a silicon chip with miniature photosensors that control an electronic circuit so that, depending on brightness, the nerve cells in the retina are stimulated to varying degrees of intensity. These send impulses via the optic nerve to the brain. The trial has now proven that the brain can actually use these signals to generate an image pattern. The implant is primarily being developed for the treatment of retinitis pigmentosa.
Learning retinal implant system
Developers: Intelligent Medical Implants
The learning retinal implant system is being developed to help restore functional vision to blind persons suffering from degenerative retinal diseases such as retinitis pigmentosa. It works by recording images of the environment with a digital camera, processing these images into electronic signals and sending them via wireless transmission to a receiver implanted in the eye. The receiver translates the signals into electric currents that are applied through micro-electrodes to the surface of the retina thereby activating the underlying ganglion cells to elicit visual perceptions in the brain.
A study enrolled 20 blind persons with retinitis pigmentosa at four European medical centres. Of these 20, 19 reported visual perception triggered by the electrical stimulation.
IMI believes the learning retinal implant system will gain CE Mark approval in 2007 with US PMA approval a year later.
Acri.Sensor mesograph system
The Acri.Sensor mesograph system, being developed through a partnership of industry, government and academic groups, is a foldable IOL with integrated pressure sensors for the continuous measurement of IOP and wireless delivery in a pair of glasses. The working principle of the device has been proven in animal experiments, but further improvements in the stability of the system are necessary before human implantation can begin.
An integrated microsystem in the IOL measures IOP, converts the data from analogue to digital format and transmits the data to a reading station built into glasses. This station also provides the energy to power the microchip by high-frequency coupling.
Currently, new prototypes are being developed for animal testing with human trials possible in late 2006 or early 2007.
Ex-PRESS miniature glaucoma shunt
The Ex-PRESS miniature glaucoma shunt, implanted under a scleral flap, provides a simplified method of filtration surgery for patients with open angle glaucoma.
Similar to trabeculectomy, the shunt reduces the intraocular pressure by diverting the aqueous humour from the anterior chamber to the subconjunctival space to form a filtration bleb. Postoperative aqueous outflow is controlled by the flow-modulating design and the scleral flap.
In a case-control comparison study, eyes that underwent trabeculectomy and those with the Ex-Press shunt implanted had nearly identical outcomes in lowering IOP but hypotony, in the early postoperative period, was less frequent in eyes that received the implant.
DeepLight gold micro-shunt
Trial results, from a study of 70 eyes with open angle glaucoma, showed there was an average of a 34% reduction in IOP compared with best medicated baseline, while complications and adverse events were minimal and transient in the majority of cases CE approval was granted in 2005 and the DMS is now available across Europe.
Developers: Carl Zeiss Meditec
Software tools can plan and measure anterior segment ocular structures including anterior chamber depth, angles and diameter. The anterior segment images can be printed with or without measurement tools and results.
The system is currently being launched across Europe and the US having received CE and FDA approval
Visucam fundus camera
Developers: Carl Zeiss Meditec
The non-mydriatic Visucam fundus camera has been designed for documenting colour photos of the back of the eye. The system has a complete PC with a database containing all images. Features include internal camera, minimum required pupil width of 3.3 mm, automatic flashlight correction and stereography. Stereo photos of the optic disk are also available in cases of glaucoma.
The product was launched across Europe and the US at the end of 2005.
The product was launched in 2005.
Developers: Heidelberg Engineering
The Slit Lamp OCT is a high resolution diagnostic instrument for non-contact analysis of morphological structures and distance measurement in the anterior chamber of the eye. The scans can be displayed either in grey-scale or false colours. The eye can be scanned from any angle simply by turning the slit lamp head and the scan itself takes just one second before it can be saved and printed. Because of its non-contact nature, pre-and postoperative examinations can be performed without the risk of infection. In addition, the slit lamp can be used independently for routine examinations.
Areas of application include refractive surgery, glaucoma, screening and diagnostic biometry.
Developers: Heidelberg Engineering
The Heidelberg Retina Tomograph 3 (HRT 3) is a confocal laser scanning system for imaging of the anterior and posterior segments of the eye. It is comprised of three modules, which can be used independently or in combination with each other.
Its major routine clinical application is analysis of the optic nerve head structure for glaucoma diagnosis. A second application is in diabetes for the location and quantification of retinal oedema. Finally, when the cornea module is added, the HRT 3 can be used as a confocal microscope for in vivo assessment of the cornea and the conjunctiva.