Faculty Bibliography

PURPOSE/OBJECTIVE:To report the long-term clinical outcome in a patient diagnosed as having bilateral progressive keratoconus who received a single corneal collagen cross-linking (CXL) treatment in the right eye and repeated CXL in the left eye. METHODS:Observational case report. Topographical changes were assessed by high-resolution Scheimpflug imaging. The right eye underwent a standard epithelium-off CXL procedure in February 2008, followed by the left eye 4 weeks later. In 2012, the left eye was treated with CXL for a second time. Irradiation was performed in all cases at a fluence of 5.4 J/cm². Energy settings were 30 minutes @ 3 mW/cm² for the CXL procedures performed in 2008, and 10 minutes @ 9 mW/cm² for the second CXL procedure of the left eye that was performed in 2012. RESULTS:The right eye that underwent a single CXL procedure showed a flattening of keratometry values between 2008 and 2012, followed by stabilization. The left eye showed a similar flattening effect between 2008 and 2012, followed by another flattening effect after the second CXL procedure and accompanied by a distinct increase in corrected distance visual acuity. CONCLUSIONS:Following repeated CXL, the corneal stroma and endothelium remained inconspicuous, and postoperative haze and visibility of the stromal demarcation line was similar to what is usually observed after a single CXL procedure. Whether the additive flattening effect of the anterior surface observed in this single case goes along with an additive increase in biomechanical stiffness remains to be seen.

BACKGROUND:Diced cartilage has been associated with several advantages and rewarding results, leading to its widespread application in various forms in rhinoplasty, but the outcomes of diced cartilage with and without tensor fascia latae wrapping have not been widely reported in evidence-based articles. OBJECTIVES/OBJECTIVE:The authors compared changes in weight, size, and histology of both bare and fascia-wrapped diced cartilage in rabbits as a model for human surgical outcomes. METHODS:One auricle from each of 15 rabbits was divided into 2 pieces, and both samples were diced. The tensor fascia latae of the rabbit was wrapped around 1 cartilage specimen from each rabbit (group A specimen); the other specimen received no wrapping (group B specimen). A group A specimen and a group B specimen were implanted into separate subcutaneous pockets in each rabbit. After 3 months, samples were removed from the recipient beds and weighed to compare pre- and postoperative weights. All specimens were examined for evidence of cartilage viability by histologic methods. RESULTS:There was a significant decrease in the weight of cartilage in group A. A nonsignificant weight increase was observed in group B. Histologic analyses of 5 parameters revealed no significant differences between the 2 groups, except for a significantly greater amount of new cartilage formation in group B. CONCLUSIONS:Any type of wrapping around diced cartilage may inhibit its access to surrounding nutrients. Dicing increases the absorption surface, which may result in some overgrowth, but wrapping may have a negative impact on the viability of the diced cartilage. LEVEL OF EVIDENCE/METHODS:4.

PURPOSE/OBJECTIVE:To evaluate the need for and quantify the extent of nomogram adjustments to compensate for potential changes in the amount of effective corneal stroma ablated in previously cross-linked corneas. METHODS:Ex vivo porcine corneas were divided into two groups (the corneal cross-linking [CXL] group, n = 30; and the control group, n = 3): these experimental corneas underwent CXL including deepithelialization, instillation of riboflavin solution for 25 minutes, and ultraviolet-A irradiation at 9 mW/cm2 for 10 minutes. The control group was deepithelialized only. Four consecutive excimer laser ablations of 50 pm each were performed (AMARIS 750S; SCHWIND eye-tech-solutions, Kleinostheim Germany), and stromal bed thickness was measured with a built-in optical coherence pachymeter. To determine the potential influence of riboflavin, a third group (the riboflavin group, n = 12) underwent deepithelialization and instillation of riboflavin, but no ultraviolet-A irradiation. RESULTS:The mean individual ablation depth across the four ablations was significantly smaller in cross-linked corneas (-17%) when compared to untreated control corneas (P < .001). A consistent reduction of 12% was observed via a cumulative analysis when assessing the relative isolated effect of CXL on the ablation rate. There was no significant effect from riboflavin in the deeper ablations, except for the first ablation (68.6 + 1.1 mm [range: 1 to 50 pm]). This may be due to a measurement error in pachymetric readings due to the thin film of riboflavin on the surface that resists even extensive rinsing. CONCLUSIONS:CXL reduces the corneal ablation depth of excimer lasers in the anterior 200 pm of the porcine cornea by approximately 12%. Further clinical studies are needed to validate these findings in human corneas.

PURPOSE/OBJECTIVE:When treating peripheral ectatic disease-like pellucid marginal degeneration (PMD), corneal cross-linking with UV-A and riboflavin (CXL) must be applied eccentrically to the periphery of the lower cornea, partly irradiating the corneal limbus. Here, we investigated the effect of standard and double-standard fluence corneal cross-linking with riboflavin and UV-A (CXL) on cornea and corneal limbus in the rabbit eye in vivo. METHODS:Epithelium-off CXL was performed in male New Zealand White rabbits with two irradiation diameters (7 mm central cornea, 13 mm cornea and limbus), using standard fluence (5.4 J/cm(2)) and double-standard fluence (10.8 J/cm(2)) settings. Controls were subjected to epithelial removal and riboflavin instillation, but were not irradiated with UV-A. Following CXL, animals were examined daily until complete closure of the epithelium, and at 7, 14, 21, and 28 days. Animals were killed and a corneoscleral button was excised and processed for light microscopy and immunohistochemistry. RESULTS:For both irradiation diameters and fluences tested, no signs of endothelial damage or limbal vessel thrombosis were observed, and time to re-epithelialization was similar to untreated controls. Histological and immunohistochemical analysis revealed no differences in the p63 putative stem cell marker expression pattern. CONCLUSIONS:Even when using fluence twice as high as the one used in current clinical CXL settings, circumferential UV-A irradiation of the corneal limbus does not alter the regenerative capacity of the limbal epithelial cells, and the expression pattern of the putative stem cell marker p63 remains unchanged. This suggests that eccentric CXL may be performed safely in PMD.

OBJECTIVE:UV-A/Riboflavin cross-linking of corneal collagen fibers (CXL) is a highly promising therapy for corneal melting in humans. A prospective interventional, nonrandomized, controlled study was conducted to compare the stabilizing effect of CXL treatment on melting keratitis in dogs and cats and the complication rate of CXL to those of standardized intensive medical treatment. PROCEDURES/METHODS:Forty-nine eyes with melting keratitis were included in the study between October 2009 and October 2012. All eyes were treated according to the same medical treatment protocol. Nineteen eyes were CXL-treated, and 30 eyes were not. Follow-up included slit-lamp examination, fluorescein staining, ulcer size measurement, stromal stability evaluation, photographic documentation, and documentation of complications. RESULTS:Five of 19 eyes in the CXL group and 9/30 eyes in the control group required rescue stabilization due to continued melting. Seven of the nine control group corneas stabilized after rescue CXL treatment. At initial presentation, the ulcers in the canine CXL group were significantly deeper and larger than in the control group. Ulcer deepening during follow-up was more pronounced in the canine control group than in the canine CXL group. CXL treatment-related complications were not observed. CONCLUSIONS:Based on the similar failure rates in the control and CXL treatment groups despite the poorer initial situation in the CXL group, the tendency for the ulcers in the control group to deepen and the stabilization of all corneas receiving CXL rescue treatment, we believe that CXL has its place as an adjunctive therapy for melting keratitis in veterinary ophthalmology.

PURPOSE/OBJECTIVE:To investigate the efficacy and safety of corneal collagen cross-linking (CXL) with photoactivated riboflavin (photoactivated chromophore for infectious keratitis [PACK]-CXL) in the management of infectious keratitis with corneal melting. DESIGN/METHODS:Prospective clinical trial. PARTICIPANTS/METHODS:Forty eyes from 40 patients with advanced infectious keratitis and coexisting corneal melting. METHODS:Twenty-one patients (21 eyes) underwent PACK-CXL treatment in addition to antimicrobial therapy. The control group consisted of 19 patients (19 eyes) who received only antimicrobial therapy. MAIN OUTCOME MEASURES/METHODS:The slit-lamp characteristics of the corneal ulceration, corrected distance visual acuity, duration until healing, and complications were documented in each group. The Mann-Whitney U test was used for statistical analysis. P values less than 0.05 were considered statistically significant. RESULTS:The average time until healing was 39.76 ± 18.22 days in the PACK-CXL group and 46.05 ± 27.44 days in the control group (P = 0.68). After treatment and healing, corrected distance visual acuity was 1.64 ± 0.62 in the PACK-CXL group and 1.67 ± 0.48 in the control group (P = 0.68). The corneal ulceration's width and length was significantly bigger in the PACK-CXL group (P = 0.004 and P = 0.007). Three patients in the control group demonstrated corneal perforation; infection recurred in 1 of them. No serious complications occurred in the PACK-CXL group. CONCLUSIONS:Corneal CXL with photoactivated riboflavin did not shorten the time to corneal healing; however, the complication rate was 21% in the control group, whereas there was no incidence of corneal perforation or recurrence of the infection in the PACK-CXL group. These results indicate that PACK-CXL may be an effective adjuvant therapy in the management of severe infectious keratitis associated with corneal melting.

PURPOSE/OBJECTIVE:To report the long-term clinical outcome of a patient diagnosed as having Terrien marginal degeneration (TMD) who was subjected to corneal collagen cross-linking (CXL) with ultraviolet-A and riboflavin in both eyes. METHODS:Topographical changes were assessed by high-resolution Scheimpflug imaging and anterior segment optical coherence tomography. Eccentric epithelium-off CXL was performed in both eyes while protecting the corneal limbus. Irradiation was performed with a fluence of 5.4 J/cm(2), using 3 mW/cm(2) for 30 minutes. RESULTS:Five years of postoperative follow-up showed regression of the keratometric values, a local thickening of the corneal stroma, and bilateral improvement of corrected distance visual acuity. CONCLUSIONS:CXL may arrest progression in TMD and even reverse the catabolic process in the corneal stroma. CXL might represent an alternative therapeutic approach for the management of TMD.

Keratoconus is a disease of the cornea that usually begins during puberty and progressively weakens its biomechanical structure. Keratoconic eyes show a conic shape and progressive thinning, both leading to irregular astigmatism and reduced vision that cannot be corrected by glasses. In early cases, special contact lens can partly compensate for the visual loss while they do not stop disease progression. Until recently, the only treatment option was a corneal transplant. In 1999, a technique called corneal collagen cross-linking (CXL) was used in human corneas suffering from keratoconus for the first time. CXL uses a process called photopolymerization to halt the progression of keratoconus with an efficacy of more than 95%. Today our challenge is to screen and identify patients early enough to offer a treatment on time before irreversible vision loss develops.

PURPOSE/OBJECTIVE:New corneal cross-linking (CXL) devices are capable of using higher UV-A light irradiances than used in original CXL protocols. The Bunsen-Roscoe law states that a photochemical reaction should stay constant if the delivered total energy is kept constant; however, little clinical data are available to support this hypothesis. METHODS:We investigated the biomechanical properties of four groups (n = 50 each) of porcine corneas. Three groups were exposed to riboflavin 0.1 % and UV-A irradiation of equal total energy (3 mW/cm(2) for 30 minutes, 9 mW/cm(2) for 10 minutes, and 18 mW/cm(2) for 5 minutes). Controls were exposed to riboflavin 0.1% without irradiation. Young's modulus of 5-mm wide corneal strips was used as an indicator of corneal stiffness. RESULTS:We observed a decreased stiffening effect with increasing UV-A intensity. Young's modulus at 10% strain showed significant differences between 3 mW/cm(2) and 9 mW/cm(2) (P = 0.002), 3 mW/cm(2) and 18 mW/cm(2) (P = 0.0002), 3 mW/cm(2) and the control group (P < 0.0001), and 9 mW/cm(2) and the control group (P = 0.015). There was no difference between 18 mW/cm(2) and the control group (P = 0.064) and between 9 mW/cm(2) and 18 mW/cm(2) (P = 0.503). CONCLUSIONS:The biomechanical effect of CXL decreased significantly when using high irradiance/short irradiation time settings. Intrastromal oxygen diffusion capacity and increased oxygen consumption associated with higher irradiances may be a limiting factor leading to reduced treatment efficiency. Our results regarding the efficiency of high-irradiance collagen cross-linking (CXL) raise concerns about the clinical efficiency of the new high-irradiance CXL devices already used in clinical practice without proper validation.