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Everything you need to know about New treatments for keratoconus

Treatment of keratoconus is at an extremely exciting stage, with new developments in cross-linking

Soosan Jacob

Posted: Monday, April 1, 2019


A: After removing donor epithelium and endothelium, CAIRS segment is punched from donor cornea using a double-bladed Jacob CAIRS trephine; B: First segment introduced into one side of the femtosecond channel using a Y-rod; C: Segment drawn in using a reverse Sinskey hook; D: Second segment similarly inserted; E: Postoperative slit-lamp appearance; F: Difference map showing flattening and regularisation of topography

As opposed to standard Dresden protocol, accelerated CXL delivers a higher irradiance for a shorter period, keeping total energy constant. It helps decrease treatment time and intraoperative dehydration while maintaining clinical efficacy. The commonly used protocol is 9mW/cm2 for 10 minutes. Higher oxygen usage during accelerated CXL can, however, lead to oxygen depletion and a decrease in the efficiency of CXL.

Pulsed CXL applies UV-A light in a pulsed manner to overcome this. Its effect is seen clinically as a deeper demarcation line and greater apoptotic effect. Further studies are required for ideal pulsing duration.

Contact lens-assisted CXL (CACXL) for thin corneas was described by the author. A riboflavin-soaked, UV barrier-free soft contact lens is placed on the de-epithelialised, riboflavin-soaked cornea to functionally increase corneal thickness before proceeding with standard/accelerated CXL (see here for more). CACXL has been shown to have adequate demarcation line and effective results in subsequent publications from various groups. It gives effective cross-linking, especially as thin corneas tend to cross-link more effectively than thicker ones due to higher oxygen bioavailability.

Customised CXL is used to obtain different curvature and flattening responses in different parts of the cornea for improving vision. Treatment can be applied in different patterns – circular, toric or arcuate. Customisation needs to be adjusted to individual biomechanical properties and would vary depending on the intraocular pressure.

Transepithelial CXL may be performed using epithelial permeability enhancers or iontophoresis to enhance riboflavin penetration through an intact cornea.

CXL combined with PTK/partial topography-guided PRK/wavefront-guided transepithelial PRK includes treatment protocols such as the Athens, Cretan and STARE-X protocols. These subtractive procedures help regularise the cornea. Combining with cross-linking helps prevent progression.

ADDITIVE TECHNOLOGIES
Synthetic intrastromal corneal ring segments (ICRS) have played a key role in the management of irregular ectatic corneas. Commercially available ones include Intacs/Kerarings/Ferrara rings/Myorings/Bisantis segments etc. Though effective, being synthetic, they have been reported to have up to 30% rate of complications including sight-threatening issues such as extrusion, migration, erosion, necrosis, corneal melts and infection.

CAIRS or Corneal Allogeneic Intra-stromal Ring Segments uses allogeneic donor corneal stromal tissue segments that are inserted into circular femtosecond dissected channels similar to Intacs. This technique was introduced by the author and retains all advantages while avoiding disadvantages of synthetic ICRS (see here). It flattens the cornea, regularises topography, centralises the cone, improves uncorrected and corrected distance visual acuity, decreases spherical equivalent, regular and irregular astigmatism and aberrations, improves quality of vision and helps decrease progression by redistributing biomechanical stress forces.

Being composed of donor cornea, it is biocompatible, can be implanted in thinner corneas, has a lower risk of complications than synthetic ICRS and can be implanted more superficially than synthetic ICRS, thus achieving greater corneal-flattening effects. It can therefore make treatment possible in a large spectrum of disease, from early to those otherwise indicated to undergo lamellar keratoplasty. Depending on other parameters, it may or may not be combined with CXL/CACXL.

CORNEAL TRANSPLANTATION
Isolated Bowman layer transplantation has been proposed by Melles et al. for strengthening the cornea. Stromal augmentation uses donut-shaped or complete lenticules implanted within the corneal stroma to correct thinning and regularise topography. However, the complexity of possible outcomes and possible further steepening in the ectatic area are disadvantages. Deep anterior lamellar keratoplasty may be needed for advanced cases of keratoconus.

Femtosecond laser-assisted DALK can create side cuts with exact depth, architecture and diameter for better wound apposition, healing and improved visual acuity. Tunnels at desired depth for air injection can facilitate big bubble formation. A lamellar cut may be created, taking care not to cut through the endothelium at the posterior cone. Intraoperative OCT makes surgery predictable and safer by assessing surgical planes, confirming big bubble, differentiating Types 1 and 2 bubbles and by verifying graft apposition.

A modified technique of pre-Descemetic DALK for primary management of acute corneal hydrops has been described by the author to avoid the scarring that occurs after currently employed management techniques. Surgery is done immediately and gives good visual, optical, topographic, refractive, structural, pachymetric and biomechanical improvement while decreasing contact lens dependence and avoiding other complications.

Primary surgery is possible by following three basic principles: oedematous stroma above Descemet’s tear should be dissected without stressing the tear; thin layers of pre-Descemetic tissue should be retained over the tear to avoid opening the anterior chamber; and the Descemet’s tear should be air tamponaded from within.

OPTICAL OPTIMISATION
Small-aperture IOLs such as the IC-8 AcufocusTM or Trinidade’s XtraFocus IOL (Morcher GmBH) work on the pinhole principle to provide clear vision through aberrated corneal optics. Agarwal et al. have described pinhole pupilloplasty with sutures for this. Complex spectacle lens design softwares have been tried but are challenging and generally not very successful in highly aberrated corneas. Pinhole glasses are available. Rigid contact lenses, hybrid lenses and scleral lenses with newer materials are being developed.

MISCELLANEOUS TREATMENTS UNDER RESEARCH
Small and strong carbon nanoparticles, though researched for strengthening the cornea, cause pigmentation. Tear fluid analysis for detecting biomarkers for keratoconus and targeted treatments such as Cyclosporine A to reduce MMP-9 and inflammatory cytokine levels are being researched to decrease progression. IVMED-80, a copper-based eye drop is also being researched for its effect on increasing lysyl oxidase activity and corneal stiffness.

Dr Soosan Jacob is Director and Chief of Dr Agarwal’s Refractive and Cornea Foundation at Dr Agarwal’s Eye Hospital, Chennai, India and can be reached at dr_soosanj@hotmail.com. She has a patent pending for shaped corneal segments and devices and processes used to manufacture them