In-vivo confocal microscopy is a novel diagnostic tool that allows ophthalmologists to visualize the cornea and other structures within the eye in high resolution. High resolution, in-vivo imaging of all five layers of the cornea removes the need for invasive, time-consuming, expensive and painful biopsies for patients. The five layers are the corneal epithelium, Bowman’s layer, stroma, Descemet’s membrane and the corneal endothelium.

Due to it being non-invasive (and by extension, not painful!), it has huge clinical potential to readily investigate numerous corneal diseases. It is already used in the detection and management of pathologic and infectious conditions, corneal dystrophies and ecstasies, monitoring contact lens induced corneal changes and for pre and post-surgical evaluation (PRK, LASIK and LASEK etc.), and penetrating keratoplasty. More recently, the nerves on the cornea have been studies to assess progression of certain diseases that damage corneal nerves – an example is diabetes.

At the time of the conception of Eyes2Eyes in 2021, and still to our knowledge today, there was no in-vivo Confocal Microscope in the Western Cape; in fact, there is only one of these microscopes in the whole of South Africa, which is privately owned in Gauteng. The ability to procure an in-vivo Confocal Microscope in public and private sector medical facilities is currently hindered by extensive costs (exceeding 1 million ZAR) from international manufacturers.

One of the core aims of Eyes2Eyes is to procure an in-vivo confocal microscope to improve the screening and diagnostic capacity Western Cape ophthalmology services.

Listed briefly below are five benefits of this technology for both ophthalmologists and patients:

1. Real-time imaging: Confocal microscopy provides real-time images of the cornea, allowing ophthalmologists to dynamically monitor changes in the cornea during an exam.
2. Early detection: By detecting corneal diseases and conditions in their early stages, in-vivo confocal microscopy can lead to earlier treatment and better outcomes for patients.
3. Non-invasive, improved diagnosis: Confocal microscopy provides high-resolution images of the cornea, allowing ophthalmologists to diagnose a range of corneal diseases and conditions with greater accuracy. In-vivo confocal microscopy is a non-invasive technique, allowing ophthalmologists to examine the cornea without the need for surgical procedures.
4. Reduced risk of complications: By avoiding invasive procedures, in-vivo confocal microscopy reduces the risk of complications for patients.
5. Better patient outcomes: With more accurate diagnosis and improved monitoring, patients are likely to receive more effective treatments, leading to better outcomes.

References

1. Tavakoli M, Hossain P, Malik RA. Clinical applications of corneal confocal microscopy. Clin Ophthalmol. 2008;2(2):435-445.
2. Petropoulos IN, Bitirgen G, Ferdousi M, et al. Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology. Frontiers in Pain Research 2021;2.

Image

Image reproduced under CC BY4.0 open access using article reference (2).

1. Minimally invasive techniques: Advances in surgical instruments and techniques are likely to lead to more minimally invasive corneal surgeries, reducing the risk of complications and improving patient outcomes. An example of this is the femtosecond laser deep anterior lamellar keratoplasty (FSDALK). Femtosecond (FS) laser is an infrared laser with a wavelength of 1053nm. Since the pulse duration is in the 10^-15 range, there is minimal damage to the surrounding tissue whilst penetrating the cornea. The DALK technique was previously discussed under “Corneal Transplants in Ophthalmology”. Essentially, with FSDALK, instead of using a circular blade or trephine to mechanically cut a circular incision in both donor and patient, “tongue and groove” patterns can be created to ensure a good fit of the graft without any slippage. This ensures good wound apposition and theoretically should reduce astigmatism. Additionally, the laser creates a wound healing reaction which also creates good adhesion, allowing earlier stitch removal. Visual recovery is faster than a traditional method of trephination.

2. Improved imaging and diagnostic tools: Advances in imaging and diagnostic technologies, such as in-vivo confocal microscopy, will allow ophthalmologists to better visualise the cornea and diagnose corneal diseases more accurately. At present, there is no in-vivo Confocal Microscope in the Western Cape; in fact, there is only one of these microscopes in the whole of South Africa, which is privately owned in Gauteng. One of the core aims of Eyes2Eyes is to procure an in-vivo confocal microscope to improve the screening and diagnostic capacity Western Cape ophthalmology services.

3. Customised treatments: With the growth of personalised medicine, corneal surgeons are likely to increasingly tailor treatments to individual patients based on their unique anatomy and medical history. Additionally, novel treatments, such as gene therapy (discussed previously on this blog) and regenerative medicine, are increasingly being researched for corneal diseases. These therapies are especially relevant in areas of the world where there is limited capacity for donor corneas. For example, Dr Heydenrych from Eyes2Eyes demonstrated the feasibility of a new growth medium that allows for the growth and proliferation of corneal cells, limbal epithelial cells, taken from previously traumatised corneas, to form cornea epithelium that could theoretically be transplanted.
4. Increased use of robotics: Robotic systems and advanced surgical instruments are likely to be increasingly used in corneal surgery, improving the accuracy and precision of procedures. The da Vinci system (Intuitive Surgical, USA) is the current standard robotic surgical system used in the field of ophthalmology. It is a telemanipulation robot that has been utilised for performing pterygium surgery in human eyes and has been successful in ex vivo corneal surgery. Telemanipulation systems are a class of robotics that enable the operator to work remotely by a computerised human—machine interface.

5. Advancements in artificial intelligence: Artificial intelligence is likely to play a growing role in corneal surgery, helping to plan surgeries, predict outcomes, and improve patient outcomes. AI has been used to predict the outcome of keratoconus management. More recently, AI-based algorithms using corneal topographies, tomographies, and Aanterior segment optical coherence tomograph (AS-OCT) such as KeratoDetect and Ectasia Status Index (ESI) have been developed to detect early keratoconus and screen patients before refractive surgeries. For the anterior segment of the eye in general, since the diseases often involve some form of imaging, including slit-lamp photography, AS-OCT, specular microscopy, corneal tomography/topography, and in vivo confocal microscopy (IVCM), there is a huge potential to leverage the power of AI to enhance the clinical service provision in these fields.

References

1. Leonard G. Heydenrych, Donald F. du Toit & Colleen M. Aldous (2016) Eviscerated Corneas as Tissue Source for Ex Vivo Expansion of Limbal Epithelial Cells on Platelet-Rich Plasma Gels, Current Eye Research, 41:12, 1543-1547.
2. Pandey SK, Sharma V. Robotics and ophthalmology: Are we there yet?. Indian J Ophthalmol. 2019;67(7):988-994.
3. Rampat R, Deshmukh R, Chen X, et al. Artificial Intelligence in Cornea, Refractive Surgery, and Cataract: Basic Principles, Clinical Applications, and Future Directions. Asia Pac J Ophthalmol (Phila). 2021;10(3):268-281.
4. Alio JL, Abdelghany AA, Barraquer R, et al. Femtosecond Laser Assisted Deep Anterior Lamellar Keratoplasty Outcomes and Healing Patterns Compared to Manual Technique. Biomed Res Int. 2015;2015:397891.
5. Sioufi K, Zheleznyak L, MacRae S, et al. Femtosecond Lasers in Cornea & Refractive Surgery. Experimental Eye Research 2021;205:108477.

Keratoconus (KC), covered in depth in our earlier blog post, is an uncommon degenerative eye condition characterised by the progressive thinning of the normally round and dome-shaped cornea. The thinning results in the formation of a cone-like bulge, typically at the centre of the cornea. If left untreated, Keratoconus can lead to significant visual impairment and potential legal blindness. The condition typically starts in adolescence or early adulthood. While the precise cause of keratoconus remains unknown, experts believe it arises from a combination of genetic and environmental factors. Various sources suggest an association between long-term eye rubbing and the development of Keratoconus, as it may change the shape of the front of the eye.

World Keratoconus Day serves as an initiative aimed at increasing awareness, providing education, and offering support to individuals living with keratoconus and their families. It instills hope for those grappling with the challenges posed by this debilitating condition. Many affected individuals, often young, find their lives significantly impacted by severe visual impairment or blindness. Unfortunately, the solution to their condition is underfunded in the public healthcare system in South Africa. This invisible disability takes a tragic toll on various aspects of life, affecting education, employment, and mental health.

The Eyes2Eyes Foundation launched a custom design Scleral Lens Programme at the Groote Schuur Cornea Clinic in June 2021. 90 young patients diagnosed with advanced keratoconus joined our programme in 16 months. A total of 102 scleral lenses have been funded for disadvantaged patients with advanced keratoconus. Scleral lenses are precision custom lenses that smoothen the optical surface to reduce the irregularities of the corneal surface. Eyes2Eyes has established a strong team of skilled professionals in South Africa and New Zealand, dedicated to world class care for patients in the Western Cape.

How can I help – right now?

• Donation to Eyes2Eyes to continue supporting the Scleral Lens Programme. Photos of the clients that we have supported can be found on our social media channels, especially our Eyes2Eyes Instagram Page
• Peruse the World KC Day Toolkit from the National Keratoconus Foundation (United States) and raise awareness of the condition through social media channels
• If you are living and affected with Keratoconus, enter the “Keratoconus & Me” photo competition run by the National Keratoconus Foundation (United States)

More information on Keratoconus can be found at the following link: https://nkcf.org/understanding-kc/

The cornea is the clear front surface of the eye. Have you ever wondered about the significance of a Cone-Shaped Cornea is, and how it could affect vision? The word keratoconus comes from the Greek words ‘keras’, meaning cornea, and ‘conus’, meaning cone, which together means ‘cone- shaped’ cornea.

Keratoconus affects all ethnicities and both sexes. The highest rates typically occur in 20- to 30-year-olds, but it is fairly common for it to be found in adolescents. It often develops in the 2^nd and 3^rd decades of life and tends to progress until the 4^th decade. While it is commonly found as an isolated eye condition, it sometimes can coexists with other eye and multi-system diseases.  

This disease is more aggressive in children than in adults and can have debilitating consequences for their vision as the condition deteriorates. Given its onset usually during their formative adolescent/adult years keratoconus can fundamentally alter the psychosocial profile of individuals. Even if their visual acuity can be corrected, patients with keratoconus are still likely to experience significant impact on their quality of life (1). The combined visual deterioration and psychological stress may debilitate patients from achieving their academic potential and contributing meaningful to their communities and economy.

Keratoconus is considered a bilateral and asymmetric (i.e. one eye is typically more severely affected than the other) (2-6) eye disease which results in the progressive thinning and steepening of the cornea leading to irregular astigmatism (i.e. irregular contouring of the cornea along its surface, affecting the way in which light enters the eye) and reduced visual acuity (i.e. less “seeing power” for the eye) (7-9). Images may also appear distorted, and the eyes may become more sensitive to glare and light.

Our understanding of the mechanism behind the development of keratoconus remains limited. The interplay between genetic and environmental factors have been associated with the cause and progression of this disease. Keratoconus progresses because of a combination of simultaneously occurring destructive and healing processes.

August was Organ Donor Awareness Month. Organ donation holds tremendous value in the field of Ophthalmology, as it offers hope and improved quality of life to many individuals suffering from vision impairment or blindness. The transplantation of corneas, the clear front surface of the eye, is the primary focus of organ donation in Ophthalmology. Corneal transplantation is a sight-saving procedure that can restore vision to those with severe corneal diseases or damage, that would otherwise result in irreversible severe visual deterioration or blindness. Corneal tissue, obtained through organ donation, replaces damaged or diseased corneas, enabling recipients to regain their sight and lead more fulfilling lives after their postoperative recovery. In the Western Cape, organ transplants are undertaken in both government and private hospitals e (e.g. heart, kidney, liver, corneal transplants).

You can hear Amanda, the founder of Eyes2Eyes, speak about her lifechanging experience of receiving a corneal transplant here as part of Cape Talk’s Gift of Life podcast series last month. Becoming an Organ Donor is very quick and you can potentially save 7 lives simultaneously. You can sign-up here in 1 minute to register as an Organ Donor.

The rest of the blog will give a little bit more detail on the types of corneal transplants. For clarity, the structure of the cornea is shown in Figure 1. Much has evolved since Eduard Konrad Zirm performed the first successful full thickness corneal transplant (penetrating keratoplasty) in a human in 1905. Various other corneal transplantation techniques now exist, collectively termed “lamellar surgery” and are also summarised below in writing and in Figure 2.

 Figure 1: Structure of the Cornea

1. Penetrating Keratoplasty (PK)

• Replacement of entire cornea thickness (epithelium, stroma, endothelium)
• Useful when there significant scarring, corneal shape changes (e.g. keratoconus with a history of hydrops), significant involvement of the back of the cornea, and ulcerations or perforations through the cornea
• Details: Compared to other techniques, it requires a longer recovery time after the operation is finished, higher risk of the body mounting an immune reaction against the transplant, higher risk of the transplant losing integrity over the course of the patient’s lifetime, higher risk of needing rigid gas permeable lenses to correct astigmatism from the transplant.

2. Deep Anterior Lamellar Keratoplasty (DALK)

• Selective replacement of the corneal stroma. The native Descemet membrane and endothelium remain in place.
• Useful when needing to replace corneal stroma in the presence of healthy endothelium, certain types of corneal stromal dystrophies, and corneal ulcers that are not full thickness.
• Details: The surgery is more complex to perform than PK, but there is less risk of endothelial rejection of the transplant, and the transplant has greater integrity because the wound size is smaller.

3. Descemet’s Stripping Automated Endothelial Keratoplasty (DSAEK)

• Selective removal of the patient’s Descemet membrane and endothelium, followed by transplantation of donor corneal endothelium and Descemet’s membrane in addition to a thin layer of posterior donor stroma to facilitate handling of the tissue.
• Useful to treat corneal oedema (in the presence of corneal dystrophies), iridocorneal endothelial syndrome, endothelial failure with prior intraocular surgery
• Details: relatively rapid healing time and visual rehabilitation (minimal change to corneal curvature); less risk of graft rejection and suture-related complications compared to PK and DALK; there is risk of postoperative graft dislocation (it is a very thin layer of tissue being transplanted … 100 – 200μm thick!).

4. Descemet’s Membrane Endothelial Keratoplasty (DMEK)

• Selective removal of the patient’s Descemet membrane and endothelium, followed by transplantation of donor corneal endothelium and Descemet’s membrane without adding stroma. This tissue graft is 10-15μm thick!!! (± x10 thinner than in DSAEK!!!).
• Useful for similar conditions to DSAEK.
• Details: offers the most rapid visual rehabilitation of any keratoplasty technique; transplants minimal tissue meaning that there is lower risk of allograft rejection and less long-term reliance on topical steroids.

5. Keratoprosthesis

• Full-thickness removal of the cornea and replacement by an artificial cornea
• Useful in patients with history of multiple failed PKs, severe keratitis and ocular surface disease resulting from limbal stem cell failure (e.g. Steven Johnson’s Syndrome) and chemical injury.

The future of corneal transplantation looks promising with advancements in surgical techniques and regenerative medicine. Laser-assisted procedures and 3D bioprinting are enhancing precision and efficiency, leading to shorter recovery times and better outcomes for patients. Laboratory grown corneas may also reduce donor tissue reliance and customization, reducing risks of rejection.

Figure 2: Schematic portraying the region of corneal tissue transplanted (red) for various modern keratoplasty techniques, including penetrating keratoplasty (PK), deep anterior lamellar keratoplasty (DALK), Descemet stripping automated endothelial keratoplasty (DSAEK), Descemet membrane endothelial keratoplasty (DMEK), and Boston Type I Keratoprosthesis (KPRO). Reproduced from University of Iowa from this link.

Acanthamoeba Keratitis

Acanthamoeba is a genus of single-celled amoeba commonly found in water and soil environments. Some species of Acanthamoeba are also capable of causing infections in animals. Some species of Acanthamoeba are also capable of causing serious infections in humans, including brain infections, skin infections, and acanthamoeba keratitis (an eye infection that targets the cornea). Acanthamoeba keratitis affects the cornea and can cause significant pain, redness, blurred vision, sensitivity to light, and the sensation of something in the eye. It is most common in people who wear contact lenses, but anyone can get the infection. It is so painful because the outermost surface of the cornea is exquisitely sensitive – it has a nerve density that is 300–600 times that of the skin! (1). To prevent this relatively rare infection, it is so important to practice good hygiene, especially when handling contact lenses. Never use tap water on your contact lenses, because acanthamoeba can be found in tap water. Acanthamoeba can also survive in chlorinated swimming pools (2) so protecting your contact lenses with goggles if you cannot take them off completely is a good idea. If left untreated, acanthamoeba keratitis it can lead to corneal ulcers, serious vision loss and even blindness. Treatment involves the use of anti-amoebic medications and may also include surgical removal of infected tissue. Early diagnosis and prompt treatment are crucial for the best outcome – seek eye care urgently.

Bottom Image: Corneal melting and new inflammatory growth of blood vessels in a patient with Acanthamoeba keratitis. They lost vision in this eye. Reproduced via open access (3)

References

1. Zander E, Weddell G. Observations on the innervation of the cornea. J Anat. 1951;85(1):68-99.
2. Kaji Y, Hu B, Kawana K, Oshika T. Swimming with soft contact lenses: danger of acanthamoeba keratitis. The Lancet Infectious Diseases. 2005;5(6):392.
3. Lorenzo-Morales J, Khan NA & Walochnik J: An update on Acanthamoebakeratitis: diagnosis, pathogenesis and treatment. Parasite, 2015, 22, 10.

Eyes are rich sensory organs (so practically speaking, they have feelings!). They eyes are happier when they are healthier – they function better and for longer, and there is less need to seek care from optometrists and ophthalmologists. Five general everyday tips are included below that could be used to keep your eyes in good health.

1. Protect your eyes from the sun

UV (ultraviolet) rays, which are given off by direct sunlight, can be harmful to your skin and eyes. If you have consistent sun exposure, without proper eye protection, there is a higher risk of developing cataracts. Certain UV rays of greater intensity are also more aggressive towards the retina. Your thin skin around your eyes can also develop skin cancer and wrinkles. Be sure to wear UV-protective sunglasses even on cloudy days.

2. Have a well-balanced, nutrient rich diet

Eating bright and colourful vegetables can help protect and fortify your eyesight. Orange carrots are full of beta carotene, which is the precursor of Vitamin A. This vitamin is a valuable antioxidant that helps reduce molecular stress and renew cells in the eyes. Oranges and peppers contain Vitamin C, Vitamin E, zeaxanthin, and lutein. These nutrients lower your risk of developing macular degeneration. Green vegetables, like broccoli, kale, lettuce, and peas, also contain valuable nutrients for your cornea and other eye structures. Some light cooking will keep most of their nutrients intact.

3. Don’t smoke

The free-radicals in tobacco smoke make smoking harmful to the eye in two main ways. Firstly, the direct irritation caused by the smoke coming into contact with the eye, which irritates and damages the cornea. The free radicals are responsible for damaging the lipids and proteins in the eyes and causing deposits to form on the surface of the eye’s lens— leading to cataract development. Secondly, there are systemic effects of smoking reduces blood oxygen, damages the blood vessels and causes widespread inflammation. The cumulative effect of this could cause damage to the insulating layer between the retina and the blood vessels that nourish it, potentially leading to degeneration of the macula, which is responsible for receiving light at the centre of the eye.

4. Take regular eye breaks

If you are concentrating on your computer or general work tasks at a desk all day, you can develop eye strain. To rest your eyes, try to concentrate on blinking – it is easy to forget when you are very focused. Try blink for three to four seconds at a time for about two minutes. This will help lubricate your eyes. The tears will cleanse your eyes to improve your focus. It is also valuable to rest your eyes completely from your tasks. For example, every 20 minutes, you could look at something 20 feet away for 20 seconds.

5. Exercise

Exercise improves blood flow throughout the body and removes waste products from all your organs. Exercise is especially good for supplying the retina and optic nerve with important nutrients so that they work optimally. Exercise is also important for corneal nourishment. Additionally, long-term exercise has the effect of reducing the pressure inside your eyes, which prevents permanent damage to your optic nerve. Without a working optic nerve, light signals will not be sent from the eye to the brain, causing vision loss. However, it is important to not be too strenuous with exercise (e.g. with very heavy weights) as this can cause damage! Equally, if you feel pain in your eyes during exercise, it is advisable to take a break and seek medical attention if the problem persists. 

1. The cornea is the clear outer layer of the eye, covering the iris and pupil. The cornea is so transparent that it’s almost invisible.
2. The cornea provides about 2/3 of the eye’s total optical power. A healthy cornea is essential for good vision, as even a small amount of damage to the cornea can significantly affect vision.
3. The cornea is avascular, meaning it contains no blood vessels. The cornea can be thought of as more resistant to infections than other parts of the eye because it has no blood vessels.
4. The cornea is made up of 5 distinct layers, including the epithelium, Bowman’s layer, the stroma, Descemet’s membrane, and the endothelium.
5. The cornea has a high number of nerve endings, making it one of the most sensitive tissues in the body.
6. The cornea is an important part of the eye’s immune defence system.
7. The cornea can be transplanted from one person to another without extensive use of immunosuppressive drugs.
8. The cornea has the ability to regenerate itself, but the process can be slow. The cornea is often used for research on wound healing and regenerative medicine.
9. Contact lenses can be made from materials that mimic the structure and function of the cornea.
10. The cornea helps to reduce glare and protects the eye from harmful UV rays. A damaged cornea can cause significant vision loss, and corneal transplant surgery may be needed to restore vision.