Faculty Bibliography

PURPOSE:To determine whether corneal cross-linking (CXL) with individualized fluence ("sub400 protocol") is able to stop keratoconus (KC) progression in ultrathin corneas with 12-month follow-up. DESIGN:Retrospective, interventional case series. METHODS:with irradiation times individually adapted to stromal thickness. Pre- and postoperative examinations included corrected distance visual acuity (CDVA), refraction, Scheimpflug, and anterior segment optical coherence tomography imaging up to 12 months after CXL. Outcome measures were arrest of KC progression at 12 months postoperatively and stromal demarcation line (DL) depth. RESULTS:(-2.06 ± 3.66 D) and densitometry (+2.00 ± 2.07 GSU). No significant changes were found in CDVA (P = .611), sphere (P = .077), or cylinder (P = .915). CONCLUSIONS:The "sub400" individualized fluence CXL protocol standardizes the treatment in ultrathin corneas and halted KC progression with a success rate of 90% at 12 months. The sub400 protocol allows for the treatment of corneas as thin as 214 μm of corneal stroma, markedly extending the treatment range. The DL depth did not predict treatment outcome. Hence, the depth is unlikely related to the extent of CXL-induced corneal stiffening but rather to the extent of CXL-induced microstructural changes and wound healing.

BACKGROUND:The corneal cross-linking (CXL) photochemical reaction is essentially dependent on oxygen and hypothermia, which usually leads to higher dissolved oxygen levels in tissues, with potentially greater oxygen availability for treatment. Here, we evaluate whether a reduction of corneal temperature during CXL may increase oxygen availability and therefore enhance the CXL biomechanical stiffening effect in ex vivo porcine corneas. METHODS:irradiance for 10 min, performed either in a cold room temperature (group 2, 4 °C) or at standard room temperature (group 4, 24 °C). Groups 1 and 3 served as non-cross-linked, temperature-matched controls. Using a stress-strain extensometer, the elastic moduli of 5-mm wide corneal strips were analyzed as an indicator of corneal stiffness. RESULTS:Accelerated epithelium-off CXL led to significant increases in the elastic modulus between 1 and 5% of strain when compared to non-cross-linked controls (P < 0.05), both at 4 °C (1.40 ± 0.22 vs 1.23 ± 0.18 N/mm) and 24 °C (1.42 ± 0.15 vs 1.19 ± 0.11 N/mm). However, no significant difference was found between control groups (P = 0.846) or between groups in which CXL was performed at low or standard room temperature (P = 0.969). CONCLUSIONS:Although initial oxygen availability should be increased under hypothermic conditions, it does not appear to play a significant role in the biomechanical strengthening effect of epithelium-off CXL accelerated protocols in ex vivo porcine corneas.

PURPOSE/OBJECTIVE:To describe a new surgical technique where corneal cross-linking (CXL) (to treat corneal ectasias) and photo-activated chromophore for keratitis-CXL (PACK-CXL) are performed while the patient is seated in an upright position at the slit lamp. METHODS:Topical anesthesia is applied in the waiting room, 10 minutes before the procedure. Once in the office or procedure room, eyelids and periorbital areas are disinfected with chloramphenicol and the patient is seated at the slit lamp. Epithelial debridement is performed with a cotton swab soaked in freshly prepared 40% ethanol, using 70 seconds of tapping, followed by gentle pressure to remove the epithelium. The patient is placed in the supine position for riboflavin application for 10 minutes. Stromal thickness is assessed using ultrasound pachymetry after 5 and 10 minutes. Finally, the patient is returned to the slit lamp to receive ultraviolet irradiation. RESULTS:CXL at the slit lamp is an easy-to-perform technique that substantially reduces the infrastructure needed to perform CXL and PACK-CXL procedures. CONCLUSIONS:A significant advantage of allowing CXL treatment at the slit lamp is that CXL technology can now be used in clinics that do not have easy access to an operating room infrastructure. Slit-lamp CXL can also reduce procedure costs by eliminating the technical fees related to the use of an operating room, making this treatment not only more accessible for patients, but also affordable. [J Refract Surg. 2021;37(2):78-82.].

PURPOSE/OBJECTIVE:To evaluate and compare corneal haze as determined by optical coherence tomography (OCT) after corneal cross-linking (CXL) for the treatment of mild to moderate keratoconus with or without mitomycin C (MMC) application. METHODS:This was a retrospective analysis of 87 eyes of 72 patients with mild to moderate keratoconus. The first group (n = 44 eyes) underwent CXL between June 2013 and January 2015 and the second group (n = 43 eyes) underwent CXL with MMC (CXL+MMC) between February and December 2015, both following the Dresden protocol. Patients were evaluated preoperatively and at 1, 3, 6, and 12 months postoperatively. Main outcome measures were corneal reflectivity and haze reflectivity measured by a specially developed OCT image analysis software. RESULTS:Anterior corneal reflectivity at 1 month and 1 year postoperatively was 14.79 ± 4.68 and 25.97 ± 15.01 (P < .001), and 13.88 ± 4.39 and 18.41 ± 9.25 (P = .025) for the CXL and CXL+MMC groups, respectively. The reflectivity of the anterior stromal haze region at 1 month and 1 year postoperatively was 23.15 ± 5.91 and 33.14 ± 16.58 (P = .005), and 20.58 ± 7.88 and 27.14 ± 12.80 (P = .049) for both groups, respectively. The changes in simulated keratometry from preoperatively to postoperatively were similar in both groups. The CXL+MMC group showed larger maximum keratometry flattening: 53.41 ± 6.88 diopters (D) preoperatively and 49.44 ± 5.66 D 1 year postoperatively versus 52.27 ± 5.78 and 50.91 ± 4.25 D for CXL alone (P = .008). CONCLUSIONS:MMC application following CXL significantly increases corneal haze. Similar studies need to be performed on simultaneous CXL and photorefractive keratectomy to evaluate the role of MMC in haze formation in such procedures. [J Refract Surg. 2021;37(2):83-90.].

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.