Comparación fluorofotométrica de la administración de riboflavina en la cámara anterior mediante aplicación corneal e instilación en el fórnix / A fluorophotometric comparison of anterior chamber riboflavin delivery via corneal application and fornix instillation

Introducción y objetivos Investigamos si la autoadministración de riboflavina por parte de los pacientes podría ser una opción viable para el cross-linking corneal (CXL), teniendo en cuenta los importantes recursos necesarios para la impregnación de la córnea. Analizamos si administrar la riboflavina en el fórnix inferior (lugar de autoadministración) resulta en concentraciones de riboflavina no menores a cuando se aplica directamente en la córnea (zona de aplicación por personal médico). Pacientes y métodos Realizamos un estudio prospectivo para evaluar las concentraciones de riboflavina en seis puntos de tiempo (basal, cinco, 15, 30, 45 y 60 minutos) en 18 voluntarios para cada uno de los dos lugares de aplicación: córnea y fórnix. Las concentraciones de riboflavina (Peschke® TE 0,25%; Peschke Trade GmbH, Huenenberg, Suiza) en la cámara anterior fueron medidas por fluorofotometría (FluorotronTM Master FM-2; OcuMetrics Inc., Mountain View, CA, EE. UU.). Resultados En los dos lugares de aplicación, córnea y fórnix, se observó una autofluorescencia de 16,7 ng/mL (desviación estándar [DE] 5,5) y 14,6 ng/mL (DE 4,6) al inicio de la serie de mediciones (p = 0,221). Después de 30 minutos, las concentraciones de fluorescencia en la cámara anterior habían aumentado a 55,1 ng/mL (DE 25,5) y a 46,1 ng/mL (DE 25,1) (p = 0,293) sin un incremento relevante adicional a los 60 minutos. Conclusiones Este estudio encontró que la aplicación de gotas de riboflavina en el fórnix inferior no fue menor a la aplicación directa en la córnea, según las mediciones fluorométricas de las concentraciones de riboflavina en la cámara anterior. Sugiere que la autoadministración es viable en términos de impregnación corneal de riboflavina (AU)

Introduction and objectives We investigated whether riboflavin self-administration by patients could be a feasible option for corneal cross-linking, given the considerable resources required to impregnate the cornea with riboflavin. We analysed whether administering riboflavin in the inferior fornix (the site of self-administration) results in non-inferior riboflavin concentrations as when applied directly on the cornea (the site of administration by medical personnel). Patients and methods We conducted a prospective study to evaluate riboflavin concentrations at six time-points (baseline, 5, 15, 30, 45 and 60min) in 18 healthy volunteers for each of two application sites: cornea and fornix. Anterior chamber riboflavin (Peschke® TE 0.25%) concentrations were measured by fluorophotometry (Fluorotron™ Master FM-2). Results For the two application sites cornea and fornix, participants did not differ in terms of age and sex. At baseline, the autofluorescence in the anterior chamber was 16.7ng/ml (SD 5.5) and 14.6ng/ml (SD 4.6) (p=0.221). After 30min, anterior chamber fluorescein concentrations had risen to 55.1ng/ml (SD 25.5) and 46.1ng/ml (SD 25.1) (p=0.293) without a further relevant increase by 60min. Conclusions This study found that applying riboflavin drops in the inferior fornix was non-inferior to applying it directly to the cornea, based on fluorophotometric measurements of anterior chamber riboflavin concentrations. This suggests that self-application of riboflavin is feasible in terms of corneal riboflavin impregnation (AU)

A fluorophotometric comparison of anterior chamber riboflavin delivery via corneal application and fornix instillation.

INTRODUCTION AND OBJECTIVES: We investigated whether riboflavin self-administration by patients could be a feasible option for corneal cross-linking, given the considerable resources required to impregnate the cornea with riboflavin. We analysed whether administering riboflavin in the inferior fornix (the site of self-administration) results in non-inferior riboflavin concentrations as when applied directly on the cornea (the site of administration by medical personnel). PATIENTS AND METHODS: We conducted a prospective study to evaluate riboflavin concentrations at six time-points (baseline, 5, 15, 30, 45 and 60min) in 18 healthy volunteers for each of two application sites: cornea and fornix. Anterior chamber riboflavin (Peschke® TE 0.25%) concentrations were measured by fluorophotometry (Fluorotron™ Master FM-2). RESULTS: For the two application sites cornea and fornix, participants did not differ in terms of age and sex. At baseline, the autofluorescence in the anterior chamber was 16.7ng/mL (SD 5.5) and 14.6ng/mL (SD 4.6) (P=.221). After 30min, anterior chamber fluorescein concentrations had risen to 55.1ng/mL (SD 25.5) and 46.1ng/mL (SD 25.1) (P=.293) without a further relevant increase by 60min. CONCLUSIONS: This study found that applying riboflavin drops in the inferior fornix was non-inferior to applying it directly to the cornea, based on fluorophotometric measurements of anterior chamber riboflavin concentrations. This suggests that self-application of riboflavin is feasible in terms of corneal riboflavin impregnation.

Fungal Keratitis: A Six-Year Review at a Tertiary Referral Centre.

Background This review reports the epidemiology, laboratory results, treatment regimens and costs of fungal keratitis at a tertiary referral center in Lucerne, Switzerland. Patients and Methods Culture-proven fungal infections between January 2010 and December 2015 were reviewed retrospectively. Results Seventeen patients with a mean age of 52 years were identified. Contact lens wear was the most important risk factor (n = 11) (65 % of all cases), with filamentous fungi being identified as the most common fungus type (n = 10) (91 % of all cases of contact lens-associated fungal keratitis). All non-contact lens-associated fungal infections (n = 6) (35 % of all cases) were related to Candida spp. Six patients (35 %) were treated on an outpatient basis; 11 cases (65 %) required hospitalisation. Systemic voriconazole was the treatment regimen prescribed most often (n = 12) (71 %), followed by topical natamycin 5 % (n = 11) (65 %). Corneal crosslinking and penetrating keratoplasty were required in 4 cases each (24 %). One case ended up in enucleation (6 %). Average costs per case were EUR 15 952 for hospitalised patients if surgical intervention was required, and EUR 7415 if no intervention was performed. Average costs for outpatients were EUR 7079. In a majority of cases, visual acuity could be improved (n = 9) (53 %) or preserved (n = 2) (12 %). Conclusion Despite the relatively low incidence of culture-proven keratitis (17 cases in 6 years), a clear pattern with regard to risk factors and fungus species was noted. In the absence of a gold standard for the treatment of fungal keratitis, the combination of systemic voriconazole and topical natamycin seems to be one of the most commonly used antifungal treatment regimens. The costs of outpatient versus inpatient non-surgical treatment were approximately the same.

[Complications of Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)]. / Komplikationen der Descemet Stripping Automatisierten Endothelkeratoplastik (DSAEK).

BACKGROUND: Lamellar keratoplasties, e.g. Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) are considered the procedures of choice for corneal endothelial diseases. In comparison to penetrating keratoplasty (PK) they are associated with faster visual rehabilitation, a lower risk of complications and a decreased necessity for follow-up visits, which reduces the burden on quality of life in elderly patients. In order to advise patients regarding the indications for surgery and to facilitate the follow-up management, it is important to know the most important complications associated with these keratoplasty techniques. RESULTS AND DISCUSSION: The most important preoperative complication is a delayed indication for the operation. In contrast to PK, DSAEK and DMEK surgery should be provided at an earlier stage of disease as chronic edema alters the stroma and reduces the speed of visual recovery. The most important complications during or early after surgery are detached lamellae, pupillary blocks with increased pressure or air bubbles in the vitreous cavity in patients with previous vitrectomy. The main long-term complications include chronic increased intraocular pressure and immune-mediated graft rejections in DSAEK patients after reducing or stopping topical corticosteroid therapy. This article describes the potential complications of endothelial keratoplasty and provides a detailed explanation of strategies to avoid these complications.

Ocular pulse amplitude as a diagnostic adjunct in giant cell arteritis.

BACKGROUND: To develop an algorithm based on the ocular pulse amplitude (OPA) to predict the probability of a positive temporal artery biopsy (TAB) result in the acute phase of suspected giant cell arteritis (GCA). METHODS: Unilateral TAB was performed and ipsilateral OPA measurements were taken by Dynamic Contour Tonometry. Among the clinical signs and laboratory findings tested in univariate analyses, OPA, Erythrocyte Sedimentation Rate (ESR) and thrombocyte count showed a strong association with a positive TAB result. Algorithm parameters were categorized into three groups (OPA >3.5, 2.5-3.5, and <2.5 mm Hg; ESR <25, 25-60, and >60 mm/h; thrombocyte count <250'000, 250'000-500'000, and >500'000/µl). Score values (0, 1, and 2) were attributed to each group, resulting in a total score range from 0 to 6. A univariate logistic regression analysis using the GCA diagnosis as the dependent and the total score as the independent variate was fitted and probability estimates were calculated. RESULTS: Thirty-one patients with suspected GCA undergoing TAB during an eighteen-month observation period were enrolled. Twenty patients showed histologically proven GCA. Four patients had score values ≤2, fourteen between 3 and 4, and thirteen of ≥5. The corresponding estimated probabilities of GCA were<7, 52.6, and >95%. CONCLUSION: The present study confirms previous findings of reduced OPA levels, elevated ESR, and elevated thrombocyte counts in GCA. It indicates that a sum score based on OPA, ESR, and thrombocyte count can be helpful in predicting TAB results, especially at the upper and the lower end of the sum score range.

Treatment options for demodex blepharitis: patient choice and efficacy.

BACKGROUND: Demodex mites are microscopic parasites that live around hair follicles or sebaceous glands and may cause chronic blepharitis. The aim of this outcome analysis was to assess the efficacy and patient preferences with regard to the currently recommended treatment options. METHODS: All patients with microscopic evidence for Demodex blepharitis were informed about the currently published treatments and instructed about daily lid hygiene. Additional topical treatment options included tea tree oil (TTO) 5%, a cleansing foam containing 0.02% TTO (Naviblef®), and metronidazole 2% ointment. Systemic treatment options included oral ivermectin 6 mg on day 1 and 14 and metronidazole 500 mg twice daily for 10 days. All patients were reviewed after 2 months for symptoms and for a mite count on 10 epilated lashes. RESULTS: Ninety-four of 96 patients with Demodex blepharitis opted for an additional treatment. The mean mite count after 2 months of treatment were 13.3 with 5% TTO (n=6), 12.0 with 0.02% TTO (n=38), 9.4 with metronidazole ointment (n=5), 12.8 with ivermectin (n=27) and 22.0 with oral metronidazole (n=5). CONCLUSION: While there are several published treatment options available, none of these options seem to be clearly effective in Demodex blepharitis.

Blood flow velocity measured using the Retinal Function Imager predicts successful ranibizumab treatment in neovascular age-related macular degeneration: early prospective cohort study.

PURPOSE: Anti-VEGF treatment has a potent vasoconstrictive effect. Early changes of retinal blood flow velocity (RBFV) measured using the Retinal Function Imager (RFI) combined with indicators of vascular status may help in predicting the visual outcome 1 month post injection in patients with neovascular age-related macular degeneration (nvAMD) under ranibizumab treatment. To develop a simple prediction model based on the change in RBFV 3 days post injection and indicators of a patient's vascular status to assess the probability of a successful visual outcome 1 month post injection. METHODS: RBFV measured using RFI were prospectively collected pre-injection and 3 days post injection in 18 eyes of 15 patients. Indicators of vascular status (history of hypertension, diabetes mellitus without retinal affection, and smoking) were assessed by medical history. By univariate analyses, parameters associated with visual outcome were weighted (-1 to 6 points). A multivariate logistic regression model with the categorized visual outcome parameter (≥0 letters gained after 1 month) as the dependent variate and the sum score as the independent variate (continuous scale) was used to estimate the score value-specific probabilities of letters gained ≥0 1 month post injection. RESULTS: The indicators of vascular status negatively influenced the likelihood of a letter gain ≥0 whereas an increase in the arterial RBFV strongly increased it. The area under the receiver operating characteristics curve for these parameters investigated was 0.71 (95% CI: 0.43-1.00). CONCLUSION: Changes in the arterial RBFV following 3 days after ranibizumab injection combined with three indicators of the vascular status identified nvAMD patients with favorable visual outcome accurately.

Diagnostic accuracy of the Amsler grid and the preferential hyperacuity perimetry in the screening of patients with age-related macular degeneration: systematic review and meta-analysis.

OBJECTIVE: To clarify the screening potential of the Amsler grid and preferential hyperacuity perimetry (PHP) in detecting or ruling out wet age-related macular degeneration (AMD). EVIDENCE ACQUISITION: Medline, Scopus and Web of Science (by citation of reference) were searched. Checking of reference lists of review articles and of included articles complemented electronic searches. Papers were selected, assessed, and extracted in duplicate. EVIDENCE SYNTHESIS: Systematic review and meta-analysis. Twelve included studies enrolled 903 patients and allowed constructing 27 two-by-two tables. Twelve tables reported on the Amsler grid and its modifications, twelve tables reported on the PHP, one table assessed the MCPT and two tables assessed the M-charts. All but two studies had a case-control design. The pooled sensitivity of studies assessing the Amsler grid was 0.78 (95% confidence intervals; 0.64-0.87), and the pooled specificity was 0.97 (95% confidence intervals; 0.91-0.99). The corresponding positive and negative likelihood ratios were 23.1 (95% confidence intervals; 8.4-64.0) and 0.23 (95% confidence intervals; 0.14-0.39), respectively. The pooled sensitivity of studies assessing the PHP was 0.85 (95% confidence intervals; 0.80-0.89), and specificity was 0.87 (95% confidence intervals; 0.82-0.91). The corresponding positive and negative likelihood ratios were 6.7 (95% confidence intervals; 4.6-9.8) and 0.17 (95% confidence intervals; 0.13-0.23). No pooling was possible for MCPT and M-charts. CONCLUSION: Results from small preliminary studies show promising test performance characteristics both for the Amsler grid and PHP to rule out wet AMD in the screening setting. To what extent these findings can be transferred to a real clinic practice still needs to be established.

Effects and adverse events after CXL for keratoconus are independent of age: a 1-year follow-up study.

PURPOSE: To compare the effect, failure rate and the risks of corneal cross-linking (CXL) in keratoconus patients aged ≥35 years to patients <35 years. METHODS: In 141 eyes of 116 keratoconus patients we compared the changes in best phoropter-corrected visual acuity (BCVA) and maximum keratometry values (Kmax) before and 12 months after CLX in patients aged ≥35 years (n=34, 38 eyes) to the cohort of patients below 35 years of age. RESULTS: Overall, CXL significantly improved BCVA from 0.487 logMAR (95% confidence interval (CI) 0.426-0.548) by -0.197 logMAR (95% CI -0.243 to -0.150; P<0.001) and reduced Kmax from 48.96 diopter (Dpt) by -1.33 Dpt (95% CI -1.85 to -0.81: P<0.001). Age ≥35 years had no effect on the changes of BCVA (-0.02 (95% CI -0.13 to 0.09); P=0.757) or Kmax (0.58 (95%CI -0.51 to 1.68); P=0.294) as compared with younger patients. In 54 patients (55 eyes, 38.5%) aged <35 years and in 18 patients (18 eyes, 47.4%) aged ≥35 years, BCVA increased by ≥2 Snellen lines. Failure (increase in Kmax ≥1 Dpt) was observed in 17 eyes (16.5%) of patients aged <35 years and in 3 eyes (7.9%) of patients aged ≥35 years during the 12-month follow-up period. Adverse outcomes (loss of ≥2 Snellen lines) occurred in 4 (3.9%) eyes of patients aged <35 years and 1 (2.6%) eye of a patient aged ≥35 years. CONCLUSION: Effects and adverse events of CXL treatment do not seem to differ between subjects younger or older than 35 years.

Central corneal regularization--optimization of uncorrected visual acuity in keratoconus patients.

BACKGROUND: Combined excimer laser correction and corneal cross-linking is a promising concept in treating keratoconus patients. Central corneal regularization represents advanced topography-guided custom ablation for ectatic corneas, aiming at correcting irregular astigmatism and at increasing the optical regularity of the corneal surface. PATIENTS AND METHODS: In a prospective single centre study, 10 keratoconus patients underwent combined treatment with corneal cross-linking and central corneal regularization by an iRES-Laser. Uncorrected visual acuity at 1 and 3 months postoperatively represented the primary endpoint. RESULTS: Mean preoperative uncorrected decimal visual acuity was 0.15 (± 0.28 standard deviation). Mean postoperative visual acuity was 0.28 (± 0.47) at one month and 0.24 (± 0.25) at three months, respectively. CONCLUSIONS: Combined corneal cross-linking and central corneal regularization treatment has the potential to achieve a clinically significant improvement of uncorrected visual acuity.