Faculty Bibliography

PURPOSE/OBJECTIVE:To evaluate the visual, refractive, and topographic outcomes of accelerated corneal collagen cross-linking (CXL) in the pediatric age group. METHODS:In this retrospective case series study, 89 eyes of 56 patients with progressive keratoconus (KCN) who were under or equal to 18 years old at the time of surgery were included. All patients underwent accelerated corneal CXL. A thorough baseline and follow-up ophthalmic examination including uncorrected distance visual acuity, best corrected visual acuity (BCVA), slit-lamp and fundus examination, and corneal tomography by Scheimpflg camera Pentacam (Oculus, Wetzlar, Germany) were performed. RESULTS:= 0.119). CONCLUSION/CONCLUSIONS:Our study shows that accelerated CXL increases visual acuity and stabilizes or improves keratometric indices in pediatric patients with progressive KCN without any serious complication for a mean follow-up time of 16 months.

Corneal cross-linking (CXL) using riboflavin and ultraviolet A (UVA) light has become a useful treatment option for not only corneal ectasias, such as keratoconus, but also a number of other corneal diseases. Riboflavin is a photoactivated chromophore that plays an integral role in facilitating collagen crosslinking. Modifications to its formulation and administration have been proposed to overcome shortcomings of the original epithelium-off Dresden CXL protocol and increase its applicability across various clinical scenarios. Hypoosmolar riboflavin formulations have been used to artificially thicken thin corneas prior to cross-linking to mitigate safety concerns regarding the corneal endothelium, whereas hyperosmolar formulations have been used to reduce corneal oedema when treating bullous keratopathy. Transepithelial protocols incorporate supplementary topical medications such as tetracaine, benzalkonium chloride, ethylenediaminetetraacetic acid and trometamol to disrupt the corneal epithelium and improve corneal penetration of riboflavin. Further assistive techniques include use of iontophoresis and other wearable adjuncts to facilitate epithelium-on riboflavin administration. Recent advances include, Photoactivated Chromophore for Keratitis-Corneal Cross-linking (PACK-CXL) for treatment of infectious keratitis, customised protocols (CurV) utilising riboflavin coupled with customised UVA shapes to induce targeted stiffening have further induced interest in the field. This review aims to examine the latest advances in riboflavin and UVA administration, and their efficacy and safety in treating a range of corneal diseases. With such diverse riboflavin delivery options, CXL is well primed to complement the armamentarium of therapeutic options available for the treatment of a variety of corneal diseases.

Before the advent of modern tomographic imaging and corneal cross-linking (CXL), diagnosis and treatment of ectatic disease were limited to disease severity where changes on the anterior corneal surface lead to visual complaints. Rigid contact lenses and/or penetrating keratoplasty addressed late stage disease, as identifying early or subclinical disease was not possible, or its need appreciated. The emergence of CXL as a viable treatment to alter the natural progression of keratoconus heightened the need for improved diagnostics.Several methods have been described in the literature to evaluate and document progression in keratoconus, but there has been no consistent definition of ectasia progression. Newer imaging techniques (ie, tomography) allowed the detection of earlier ectatic disease, before visual loss and subjective complaints. The Belin ABCD classification/staging system was introduced on a Scheimpflug imaging system [Pentacam, (Oculus GmbH, Wetzlar, Germany)] to address previous shortcomings. The ABCD system utilizes 4 parameters: Anterior ("A") and posterior ("B" for Back) radius of curvature taken from a 3.0 mm optical zone centered on the thinnest point, "C" is minimal Corneal thickness, and "D" best spectacle Distance visual acuity. The first 3 parameters (A, B, C) are machine-generated objective measurements that can be used to determine progressive change.The staging system is not limited to a specific commercial entity and can be incorporated in any tomographic imaging system. The ABCD Progression Display graphically displays each parameter and shows when statistical change above measurement noise is reached. This should allow the clinician the ability to diagnose progressive disease at a much earlier stage than was previously possible, with the confidence that earlier intervention could prevent visual loss.

PURPOSE:To determine the impact of corneal crosslinking (CXL) performed over the laser in situ keratomileusis (LASIK) flap using the Standard CXL (S-CXL) protocol or under the flap after flap lift (flap-CXL) on regional corneal stiffness using Brillouin microscopy. SETTING:University of Southern California Keck School of Medicine, Los Angeles, California, and Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA. DESIGN:Laboratory ex vivo experiment. METHODS:After epithelium debridement, LASIK flaps were created on intact fresh porcine eyes with a mechanical microkeratome. Then, S-CXL (riboflavin applied to the corneal surface followed by 3 mW/cm ultraviolet exposure with the flap in place for 30 minutes) or flap-CXL (riboflavin applied to the stromal bed after reflecting the flap followed by the same ultraviolet A exposure with the flap replaced) was performed. Depth profile of stiffness variation and averaged elastic modulus of anterior, middle, and posterior stroma were determined by analyzing Brillouin maps. Each eye served as its own control. RESULTS:The study was performed on 24 fresh porcine eyes. S-CXL had maximal stiffening impact in the anterior most corneal stroma within the LASIK flap (8.40 ± 0.04 GHz), whereas flap-CXL had lower maximal stiffening impact (8.22 ± 0.03 GHz) (P < .001) that occurred 249 ± 34 μm under the corneal surface. S-CXL increased longitudinal modulus by 6.69% (anterior), 0.48% (middle), and -0.91% (posterior) as compared with flap-CXL, which increased longitudinal modulus by 3.43% (anterior, P < .001), 1.23% (middle, P < .1), and -0.78% (posterior, P = .68). CONCLUSIONS:The S-CXL technique generated significantly greater stiffening effect in the anterior cornea than a modified protocol with riboflavin administration under the flap (flap-CXL). Minimal stiffening occurred in the middle or posterior cornea with either protocol.

PURPOSE/OBJECTIVE:Photoactivated chromophore for keratitis cross-linking (PACK-CXL) is used as an adjunct therapy to antibiotic medication in infectious keratitis. This experimental study aimed at quantifying the PACK-CXL efficacy as a function of UV fluence using several bacterial strains and irradiated volumes. METHODS:Six distinct bacterial strains, including standardized strains and clinically isolated strains from patients with keratitis, were analyzed. Bacterial concentrations between 10 and 10 cells/mL were used (simulating small corneal ulcers). Volumes of either 11 μL (≈285 μm stromal thickness) or 40 μL (≈1000 μm stromal thickness) were irradiated within a microtiter plate at different fluences (5.4-27 J/cm) and irradiances (3, 9 and 18 mW/cm). The ratio of bacterial killing (B†) was determined to evaluate the antimicrobial efficacy of PACK-CXL. RESULTS:B† was similar (51 ± 11%) in bacterial concentrations between 10 and 10 per ml. In 11 μL volume, Staphylococcus aureus (SA) 8325-4 ATCC 29213, Bacillus subtilis (BS) 212901, and Pseudomonas aeruginosa (PA) 2016-866624 were most sensitive to PACK-CXL at 5.4 J/cm (on average B† = 49 ± 8%), whereas Klebsiella oxytoca (KO) 2016-86624 (B† = 25%) was least sensitive. When irradiating a larger volume, B† was on average lower in 40 μL (19 ± 18%), compared with 11 μL (45 ± 17%, P < 0.001). By contrast, applying a higher UV fluence increased B† of SA ATCC 29213, from 50% at 5.4 J/cm to 92% at 10.8 J/cm, to 100% at 16.2 J/cm and above. CONCLUSIONS:Applying higher UV fluences substantially increases the bacterial killing rates. Safety limits for clinical application require further investigation.