Robert P.L. Wisse

Nationwide reduction in the number of corneal transplantations for keratoconus following the implementation of cross-linking.

Keratoconus is characterized by corneal ectasia and irregular astigmatism, which can lead to diminished vision and corneal scarring. Approximately 10–20% of patients with keratoconus eventually require a corneal transplant. Corneal cross‐linking (CXL) is a relatively new treatment that may help prevent the need for corneal transplantation. Here, we investigated whether the introduction of CXL has reduced the number of corneal transplants performed annually.

Cytokine Expression in Keratoconus and its Corneal Microenvironment: A Systematic Review

Keratoconus (KC) is a progressive corneal ecstasia characterized by thinning and weakening of the cornea that leads to a cone-like appearance, scarring, and decreased vision. Despite the well-described clinical signs, the cause of KC is unknown. Nevertheless, various genes, proteinases, and environmental factors (eye-rubbing, contact lens wear, tear film composition) have been implicated in its etiology. Although classically defined as a predominantly degenerative disease, with mechanically induced trauma accelerating its course, accumulating evidence suggests a pivotal role for inflammation in the pathophysiology of KC. Several reports have linked various inflammatory mediators (cytokines) with KC, but with contradictory findings. The methods and materials used in these studies vary considerably and warrant critical evaluation to decipher the role of inflammatory mediators in KC. We performed a systematic review of current literature on cytokine expression studies in KC and discuss critical soluble and cellular inflammatory mediators that are implicated in its pathogenesis.

Foveal Cone-Photoreceptor Integrity in Aging Macula Disorder

PURPOSE To establish the relation between AMD stage and a quantitative measure for the integrity of foveal cone photoreceptors related to the optical Stiles-Crawford effect. METHODS Fifty-six AMD eyes and 57 control eyes were included in the final analysis. AMD was graded in accordance with the International Classification System into five mutually exclusive stages. Stages 0 to 1 were labeled no AMD, stages 2 to 3 were labeled early AMD, and stage 4 was labeled late AMD. Fundus reflectometry, together with a model-fit procedure, provided information on directional cone reflectance (Rd), a quantitative measure for the integrity of foveal cone photoreceptors. Optical densities of macular pigment (MPOD) and melanin (MOD) were also obtained. A general linear model analysis was used to compare Rd, MPOD, and MOD among the AMD stages. RESULTS Mean Rd was lower in early AMD (0.92%, P < 0.001) and late AMD (0.86%, P < 0.001) compared with mean Rd in the no-AMD stage (1.76%). Mean MPOD was not different in early AMD (0.53, P = 0.05), but it was lower in late AMD (0.19, P < 0.001) compared with mean MPOD in the no-AMD stage (0.42). Mean MOD was lower in early (1.09, P = 0.001) and late (1.01, P = 0.004) AMD compared with mean MOD in the no-AMD stage (1.23). CONCLUSIONS Foveal cones show signs of misalignment and/or outer segment deterioration in early AMD. Melanin rather than macular pigment may play a protective role against AMD, although loss of these ocular pigments can also be caused by AMD.

Corneal Cross-Linking for Pediatric Keratoconus: Long-Term Results.

Purpose: To assess the efficacy and safety of cross-linking in pediatric patients with keratoconus and to provide a systematic literature overview regarding this subject. Methods: In this prospective cohort, 54 eyes of 36 pediatric patients with keratoconus underwent standard epithelium-off cross-linking. Follow-up measurements taken up to 5 years after treatment were compared with baseline values. Logistic regression was used to identify the underlying cause in case of progression despite treatment. Finally, a systematic search was performed in PubMed and Embase, and data were extracted and summarized. Results: At all follow-up visits up to 5 years, maximum keratometry values improved significantly (mean change at 5 years −2.06 diopters (D), P = 0.01); moreover, average keratometry, uncorrected distance visual acuity, and corrected distance visual acuity improved at all follow-up times, though not always to the level of statistical significance. In 12 eyes (22%), keratoconus had progressed by ≥1.0 D by the last follow-up visit, despite corneal cross-linking. Cones that were more decentralized were identified as the underlying cause of disease progression. The systematic search yielded 17 unique articles: 10 articles on epithelium-off cross-linking, 2 on accelerated cross-linking, 2 on transepithelial cross-linking, 1 on both epithelium-off and transepithelial cross-linking, and 2 on transepithelial cross-linking with iontophoresis. Conclusions: Our long-term follow-up reveals that epithelium-off cross-linking is both apparently safe and effective when used to prevent keratoconus progression in pediatric patients. However, disease progression occurred in 22% of the treated eyes; this progression was attributed to a more decentralized cone location.

A multivariate analysis and statistical model for predicting visual acuity and keratometry one year after cross-linking for keratoconus.

PURPOSE To investigate putative prognostic factors for predicting visual acuity and keratometry 1 year following corneal cross-linking (CXL) for treating keratoconus. DESIGN Prospective cohort study. METHODS This study included all consecutively treated keratoconus patients (102 eyes) in 1 academic treatment center, with minimal 1-year follow-up following CXL. Primary treatment outcomes were corrected distance visual acuity (logMAR CDVA) and maximum keratometry (K(max)). Univariable analyses were performed to determine correlations between baseline parameters and follow-up measurements. Correlating factors (P ≤ .20) were then entered into a multivariable linear regression analysis, and a model for predicting CDVA and K(max) was created. RESULTS Atopic constitution, positive family history, and smoking were not independent factors affecting CXL outcomes. Multivariable analysis identified cone eccentricity as a major factor for predicting K(max) outcome (ß coefficient = 0.709, P = .02), whereas age, sex, and baseline keratometry were not independent contributors. Posttreatment visual acuity could be predicted based on pretreatment visual acuity (ß coefficient = -0.621, P < .01, R(2) = 0.45). Specifically, a low visual acuity predicts visual improvement. A prediction model for K(max) did not accurately estimate treatment outcomes (R(2) = 0.15). CONCLUSIONS Our results confirm the role of cone eccentricity with respect to the improvement of corneal curvature following CXL. Visual acuity outcome can be predicted accurately based on pretreatment visual acuity. Age, sex, and K(max) are debated as independent factors for predicting the outcome of treating keratoconus with CXL.

Trends in penetrating and anterior lamellar corneal grafting techniques for keratoconus: a national registry study

Keratoconus is a progressive disorder and one of the primary indications for corneal transplantation. Anterior lamellar keratoplasty offers several advantages over other techniques, including endothelial preservation and longer graft survival. In this study, we examined the recent trend of using lamellar techniques for keratoconus at a national level.

Bandage and scleral contact lenses for ocular graft-versus-host disease after allogeneic haematopoietic stem cell transplantation

Editor, O cular graft-versus-host disease (GvHD) is a frequent complication of allogeneic haematopoietic stem cell transplantation (allo-SCT), occurring in 40–80% of the patients. Keratoconjunctivitis sicca (KCS) is the most common manifestation of ocular GvHD and can lead to severe cases of punctate and filamentary keratitis, causing invalidating discomfort, irreversible ocular surface damage and visual loss (Takahide et al. 2007; Schornack et al. 2008). Gas permeable soft bandage lenses (BL) and rigid scleral lenses (SL) have been increasingly available and can be additionally used in severe ocular GvHD when conventional therapy is insufficient (Jacobs & Rosenthal 2007; Russo et al. 2007). Our single-centre retrospective noncomparative cohort study included forty eyes of 21 adult patients with ocular GvHD after allo-SCT between 2008 and 2013 unresponsive to conventional therapy (lubrication, immunosuppressants and/or modulants) who received same BL and/or SL treatment in both eyes. To investigate the lenses’ effectiveness and adverse effects in ocular GVHD, we collected data from demographic, medical, haematological and ophthalmological records. Three types of silicon hydrogel bandage lenses were used as follows: (i) PureVision (Bausch en Lomb, Rochester, NY, USA) (Balafilcon-A), (ii) Biofinity (Cooper Vision, Pleasanton, CA, USA) (Comfilcon-A) and (iii) Air-Optix Night and Day (Ciba Vision, Corp.) (LotrafilconA), and fitted as daily and/or day/night wear. A scleral lens Procornea (Eerbeek, the Netherlands) was fitted as daily wear in patients with more severe corneal surface irregularity when epithelial defects failed to improve during BL use, or when optical correction for irregular astigmatism was needed. Clinical evaluation and replacement of new BLs was performed monthly. Successful effect of the contact lens wear or therapy was based on the objective findings of ocular GvHD (clinical symptoms, reduced fluorescein staining classified according to the Oxford Index for staining and tear film break-up time (BUT). Adverse effects were defined as lens-related negative ocular effects that resulted in discontinuation of therapy. The number of patients in our study was limited; however, we had a long median follow-up period of 5 year and no selection bias (see Table S1). Following the local step-up treatment plan, the cases refractory to various local and systemic medications were fitted with BL first (n = 20) and when unsuccessful with SL (n = 9). One patient received SL primarily, two received additional SL wear simultaneouswith BL. Two patients wearing BL failed SL. Ocular GvHD patients after alloSCT showed a 55% (n = 11/20) successful effect of clinical signs using BL. The Oxford Index score of grading staining, however, showed significant improvement at the evaluation end-point of BL wear (p = 0.009) and also at last SL follow-up compared to the score at SL placing (p = 0.001). All patients with BL and SL still used topical lubrication; however, we found that the number of the eye drops used was lower. The most common reasons of unsuccessful therapy were either no or insufficient resolution of corneal/ conjunctival staining (n = 7/20) or termination due to adverse effects and/ or general intolerance to the contact lens (n = 2/20). The total prevalence of infectious adverse effects leading to discontinuation of BL or SL lens wear was 14% (n = 3/21): herpetic keratitis (n = 2, 1 BL and 1 SL) and Pseudomonas keratitis (1 BL). Furthermore, two patients had subconjunctival haemorrhage (1 BL and 1 SL). No other adverse events, such as abrasions, neovascularization and papillary conjunctivitis, were observed during BL or SL wear. We conclude that both BL and SL can be efficient treatment modalities that protect the cornea, accelerate the healing process and decrease the frequency of topical lubricant administrations. We advise that patients should be instructed on the risk of infectious keratitis and regularly controlled. The close collaboration of contact lens specialist and ophthalmologist offers a consistent treatment modality that is beneficiary for the patient. Our results illustrate that BL and SL are a therapeutic modality that could be considered in the management of severe dryness-related epitheliopathy associated with ocular GvHD.

Does lamellar surgery for keratoconus experience the popularity it deserves

To analyse developments in surgical treatment for keratoconus (KC) by assessing rates and types of corneal surgery from 2005 to 2010.

Higher-order aberrations 1 year after corneal collagen crosslinking for keratoconus and their independent effect on visual acuity.

Purpose To evaluate the effect of corneal collagen crosslinking (CXL) in progressive keratoconus patients on higher‐order aberrations (HOAs) and the effect of change in HOAs on visual acuity between baseline and 1 year after CXL. Setting Tertiary academic referral center, Utrecht, the Netherlands. Design Prospective cohort study. Methods This study included consecutive keratoconus patients who were treated with epithelium‐off CXL and followed for a minimum of 1 year. The following corneal HOAs were measured with Scheimpflug tomography (Pentacam HR type 70900): coma, trefoil, spherical aberration, and total corneal HOAs. A 2‐tailed paired‐samples t test was used to compare baseline and postoperative aberrations. Multivariable linear regression was applied to assess the independent effects of HOA subtypes on changes in uncorrected (UDVA) and corrected (CDVA) distance visual acuity. Results Overall, the degree of corneal HOAs in the patient cohort (N = 187) was relatively unchanged after CXL, with a mean change of −1.34% (P = .272). Horizontal coma contributed most to the total amount of HOAs but was virtually unchanged on average. The HOA subtype of spherical aberrations decreased significantly (−15.68%) (P < .001). There was no effect of the change in HOAs on the change in CDVA; however, there was a significant effect of the change in horizontal coma on the change in UDVA (P = .003; B −0.475). Conclusions Corneal HOAs in general were relatively unchanged from baseline to 1 year after CXL in eyes with progressive keratoconus. A change in horizontal coma had a strong and independent effect on UDVA. Financial Disclosure None of the authors has a financial or proprietary interest in any material or method mentioned.

Corneal depositions in tyrosinaemia type I during treatment with Nitisinone.

We present a 17-year-old boy, diagnosed with tyrosinaemia type I at an age of 7 months, with new complaints of severe intermittent photophobia and burning eyes. His tyrosinaemia type I is treated with nitisinone and a protein-restricted diet. Dietary compliance is low since he entered puberty. His ocular complaints are attributable to subepithelial corneal deposits, resembling the common corneal phenotype of tyrosinaemia type II. Serum tyrosine levels were markedly elevated. Tyrosinaemia is a metabolic disease of tyrosine metabolism, subdivided into two types. Corneal deposits and photophobia are cardinal features of untreated tyrosinaemia type II, but not of type I. Novel treatment strategies (with nitisinone) for type I tyrosinaemia lead to a phenotype comparable with type II, including these corneal deposits. At follow-up visits his ocular complaints unfortunately remained unchanged, though he states his dietary compliance improved through the years.