Claude Kaufmann

Voriconazole Concentration in Human Aqueous Humor and Plasma during Topical or Combined Topical and Systemic Administration for Fungal Keratitis

ABSTRACT Voriconazole (VRC) is an antifungal drug that effectively treats keratitis caused by yeasts and molds when administered orally. We retrospectively evaluated clinical outcomes and plasma and aqueous humor drug concentrations in five patients with fungal keratitis and one patient with posttraumatic endophthalmitis who were treated with VRC. VRC was administered either topically (1% eye drops every hour) or orally (400 mg twice a day). Plasma and aqueous humor samples from affected eyes were taken 12 h after oral administration or 1 h after eye drop application. The drug concentration was measured by liquid chromatography with UV or mass spectrometric detection. All six patients responded well to VRC treatment. The VRC concentration ranged from 2.93 to 3.40 mg/liter in the aqueous humor and from 3.20 to 4.20 mg/liter in the plasma after combined oral and topical treatment. Topical administration alone resulted in highly variable trough VRC concentrations of 0.61 to 3.30 mg/liter in the aqueous humor. VRC concentrations were above the MIC for Candida albicans Aspergillus fumigatus and clinical improvement was seen in all four patients with C. albicans and A. fumigatus keratitis. Combined orally and topically administered VRC resulted in aqueous humor drug concentrations of ≥2.93 mg/liter, which is above the VRC MIC for most fungi. Topical VRC treatment resulted in an aqueous humor drug concentration >0.61 mg/liter, which is above the MIC for most Candida species. The results from this small series of patients suggest that both topical and combined systemic and topical VRC therapy can be effective in treating fungal keratitis. Furthermore, the data provide preliminary support for initiation of VRC treatment with a combined topical and systemic administration until the causative fungus and its MIC are identified.

Comparison and reproducibility of corneal thickness and curvature readings obtained by the Galilei and the Orbscan II analysis systems

PURPOSE: To compare central corneal thickness (CCT) and keratometry readings using the Galilei dual Scheimpflug analyzer, the Orbscan II anterior segment analysis system, and the Sonogage ultrasound (US) pachymeter. SETTING: Lucerne Eye Clinic, Cantonal Hospital, Lucerne, Switzerland. METHODS: In a prospective single‐center study, 85 eyes of 45 healthy volunteers were examined with the Orbscan II and Galilei systems in random order followed by Sonogage US pachymetry. The CCT and keratometry measurements were compared using a paired t test. To assess the intraobserver and interobserver reproducibility of the 2 keratometers, 9 volunteers were examined 3 times by 4 independent observers and the intraclass correlation coefficient (ICC) was calculated. RESULTS: The mean CCT was 551.7 μm ± 36.6 (SD) with the Galilei, 554.8 ± 45.1 μm with the Orbscan II, and 558.5 ± 38.4 μm with the Sonogage. The CCT readings of the Galilei and Orbscan II did not differ significantly (P = .12). The mean keratometry readings with the Galilei and Orbscan II were similar, although both the steep (Ks) and flat (Kf) axes tended to be flatter with the Galilei system. The ICCs for CCT, Kf, and Ks were high with both keratometers (0.98, 0.97, 0.84 for Galilei and 0.97, 0.96, 0.95 for Orbscan II, respectively), indicating that variation in measurements was mainly due to true subject‐to‐subject variation rather than observer error. CONCLUSION: Keratometry and pachymetry readings with the Galilei and Orbscan II systems showed good concordance and high reproducibility, which would allow the examinations to be delegated to nonmedical personnel.

Use of Intraoperative Fourier-Domain Anterior Segment Optical Coherence Tomography During Descemet Stripping Endothelial Keratoplasty

PURPOSE To evaluate the intraoperative use of handheld Fourier-domain optical coherence tomography (OCT) during Descemet stripping automated endothelial keratoplasty (DSAEK) to assess the donor-host interface. DESIGN Prospective, observational case series. METHODS Six patients undergoing DSAEK surgery were included. OCT scans of the cornea were performed intraoperatively after insertion of the donor disc, after instillation of air in the anterior chamber beneath the disc, after vent incisions in the host cornea in each quadrant, following air-fluid exchange at the end of operation, and on day 1 after surgery. The central 3 mm of each cornea was scanned. The broadest gap between donor and host cornea (interface space) was measured. RESULTS Adequate readings could be obtained from all patients without any complications. In 2 patients there was a decrease in the width of the interface space after each surgical step documented by the OCT scans. At the end of their operation, no interface space was detectable. In 2 patients, interface space disappeared after the vent incisions and did not reappear during the further course of the surgery. In further 2 patients the separation between the host and donor was still detectable at the end of the operation. All patients had no detectable interface gap on day 1. CONCLUSIONS Handheld anterior segment OCT can be used to assess the host-donor interface in lamellar corneal transplantation surgery. Donor adherence can occur in spite of residual interface space at the end of surgery. Further studies should be conducted to answer the question of which surgical steps are useful in assisting with donor adhesion.

Corneal Cross-Linking as Supplementary Treatment Option in Melting Keratitis: A Case Series

BACKGROUND Corneal melting represents a serious condition that can result in corneal perforation and loss of vision. Treatment options include topical and systemic immunosuppression, cyanoacrylate gluing, and emergency keratoplasty, depending on the underlying disease and the stage of corneal melt. Recently, corneal cross-linking (CXL) has emerged as an additional treatment option. The present study evaluates whether CXL induces a clinical improvement in melting keratitis not responding to conventional treatment. HISTORY AND SIGNS Six patients undergoing CXL for corneal melting of variable origin (including bacterial, fungal and Acanthamoeba keratitis) were reviewed retrospectively. THERAPY AND OUTCOME Treatment parameters included riboflavin application following UV irradiation with a wavelength of 370 nm and an irradiance of 3 mW/cm2 for 30 minutes. Four patients with corneal melting due to contact lens-related infectious keratitis showed healing without any need for further interventions up to date. In two patients, CXL stabilized the melting cornea and facilitated additional surgical procedures. CONCLUSIONS By stabilizing corneal collagen fibres, CXL seems to represent an effective option to re-establish corneal integrity in the event of pending perforations. In established perforations, CXL facilitates further emergency procedures by stiffening the tissue.

Astigmatic neutrality in biaxial microincision cataract surgery.

PURPOSE: To assess the astigmatic effect of biaxial microincision cataract surgery (MICS) with insertion of an UltraChoice 1.0 Rollable Thinlens intraocular lens (IOL) in a sufficiently powered controlled study. SETTING: Queen Elizabeth Hospital, South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, Australia. METHODS: Consecutive patients having biaxial MICS were evaluated prospectively. Keratometry was performed preoperatively and postoperatively. Vector analysis of the alteration in the keratometric cylinder was compared with that in control eyes not having surgery but having keratometry over a similar time frame. RESULTS: There were 76 eyes in the surgical group and 74 in the control group. The right‐hand incision used for IOL insertion had a mean external opening width of 2.00 mm and a mean internal width of 1.89 mm. The left‐hand incision measured a mean of 1.49 mm and 1.46 mm, respectively. There was no statistically significant difference between the surgical group and the routine variability in keratometry in the untreated control group in surgically induced astigmatism (surgical group, 0.57 diopter [D] ± 0.05 [SEM]; control group, 0.54 ± 0.06 D; P =.660) or the degree of mean calculated flattening effect at the right‐hand incision (0.01 ± 0.06 D and −0.05 ± 0.05 D, respectively; P = .405) or at the left‐hand incision (−0.06 ± 0.05 D and 0.03 ± 0.06 D, respectively; P = .283). CONCLUSION: Biaxial MICS with insertion of IOL through a temporal incision of 2.0 mm offers prospects of astigmatic neutrality in cataract surgery.

ISRCTN12125882 - Influence of topical anti-VEGF (Ranibizumab) on the outcome of filtration surgery for glaucoma - Study Protocol

BackgroundExcessive wound healing, with scarring of the episcleral tissue or encapsulation of the filtering bleb is the main reason for failure in trabeculectomy. Ranibizumab, an inhibitor of the Vascular Endothelial Growth Factor (VEGF), is seen as a promising candidate to prevent or treat extensive wound healing. We describe the design of a two phased study, i) assessing the local tolerability and safety of topical ranibizumab and ii) assessing the efficacy of topical ranibizumab against placebo in patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and intra ocular lens (IOL) implantation.Methods/DesignIn the first phase five patients that had trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be treated with topical ranibizumab (Lucentis®) eye drops (2 mg/ml) four times daily for one month. The treatment will be started at the first postoperative day. Patients will be assessed for local and systemic side effects using a standardised schedule. In the second phase, after successful completion of phase 1, consenting eligible patients who underwent trabeculectomy with mitomycin C combined with phacoemulsification and IOL implantation will be randomised to either receive topical ranibizumab eye drops (2 mg/ml) four times daily for 1 month or placebo (BSS 4x/d for 1 month). Patients will be reviewed weekly for 4 weeks until conjunctival sutures are removed. Further follow up examinations are planned after 3 and six months. Assessment of differences in the intraocular eye pressure will be considered primary, and bleb appearance/vascularisation using a standardized photography and the Moorfields bleb grading system, postoperative intraocular pressure and conjunctival wound healing problems will be considered secondary outcome parameters.DiscussionAnti-VEGF-antibodies might be more effective in preventing scaring and might have fewer toxic side effects than the currently used anti-metabolites and may replace them in the long term.Trial RegistrationISRCTN: ISRCTN12125882

Rapid detection of fungal keratitis with DNA-stabilizing FTA filter paper.

Purpose. Polymerase chain reaction (PCR) is increasingly important for the rapid detection of fungal keratitis. However, techniques of specimen collection and DNA extraction before PCR may interfere with test sensitivity. The purpose of this study was to investigate the use of DNA-stabilizing FTA filter paper (Indicating FTA filter paper; Whatman International, Ltd., Maidstone, UK) for specimen collection without DNA extraction in a single-step, nonnested PCR for fungal keratitis. Methods. Specimens were collected from ocular surfaces with FTA filter discs, which automatically lyse collected cells and stabilize nucleic acids. Filter discs were directly used in single-step PCR reactions to detect fungal DNA. Test sensitivity was evaluated with serial dilutions of Candida albicans, Fusarium oxysporum, and Aspergillus fumigatus cultures. Test specificity was analyzed by comparing 196 and 155 healthy individuals from Switzerland and Egypt, respectively, with 15 patients with a diagnosis of microbial keratitis. Results. PCR with filter discs detected 3 C. albicans, 25 F. oxysporum, and 125 A. fumigatus organisms. In healthy volunteers, fungal PCR was positive in 1.0% and 8.4% of eyes from Switzerland and Egypt, respectively. Fungal PCR remained negative in 10 cases of culture-proven bacterial keratitis, became positive in 4 cases of fungal keratitis, but missed 1 case of culture-proven A. fumigatus keratitis. Conclusions. FTA filter paper for specimen collection together with direct PCR is a promising method of detecting fungal keratitis. The analytical sensitivity is high without the need for a semi-nested or nested second PCR, the clinical specificity is 91.7% to 99.0%, and the method is rapid and inexpensive.

Treatment of traumatic corneal abrasions: a three-arm, prospective, randomized study.

Purpose: To compare three different treatment modalities for traumatic corneal abrasions. Methods: We conducted a prospective, randomized, masked, three-arm clinical study of patients presenting with superficial corneal foreign bodies. Treatment modalities were: (1) pressure patching with ofloxacin ointment (patch group, PG, n = 18), (2) therapeutic contact lens with ofloxacin eye drops (contact lens group, CLG, n = 20) and (3) ofloxacin ointment alone (ointment group, OG, n = 28). Primary outcome measure was the difference of the mean corneal abrasion area between the three groups at 3 different time points (baseline, day 1 and day 7). Results: A total of 66 patients were included in the study over a period of 2 years. Mean initial corneal abrasion area was 3.6 ± 3.4 mm2 in the PG, 4.2 ± 4.0 mm2 in the CLG and 3.7 ± 3.1 mm2 in the OG (p = 0.875). Differences in corneal abrasion area at any time point were not statistically significant (abrasion area decrease from presentation to day 1 was 3.4 ± 3.3 mm2 in the PG, 4.1 ± 4.0 mm2 in the CLG and 3.5 ± 3.1 mm2 in the OG, p = 0.789). The epithelium was healed in all patients at day 7. Conclusions: Treating traumatic corneal abrasions by pressure patching, a bandage contact lens or ointment alone was equal in reducing the abrasion area or reducing pain. According to our results the treatment of choice for traumatic abrasions may be adapted to the needs and preferences of the patient.

Comparison of dynamic contour tonometry with Goldmann applanation tonometry following Descemet's stripping automated endothelial keratoplasty (DSAEK)

BACKGROUND Intraocular pressure (IOP) measurements using Goldmann applanation tonometry (GAT) are influenced by central corneal thickness (CCT) whereas dynamic contour tonometry (DCT) allows for IOP measurements independent of CCT. After Descemets stripping automated endothelial keratoplasty (DSAEK) the CCT is, compared to healthy eyes, increased. The objective of this prospective study was to compare IOP measurements obtained by DCT and GAT in patients after a DSAEK procedure. PATIENTS AND METHODS DCT and GAT were performed 3 and/or 6 months after DSAEK. Comparison of means was performed using the Wilcoxon signed-ranks test. RESULTS In total, 50 IOP measurements on 33 eyes were obtained. Mean CCT was 621 (+/- 60) microm. Overall correlation between GAT and DCT was good, however, in some patients a remarkable difference between pressure readings of up to 10.8 mmHg was observed. Mean IOP readings obtained by DCT were significantly higher (20.9 +/- 5.9 mmHg) than those obtained by GAT (19.1 +/- 6.5 mmHg; p = 0.0002). However, the difference between GAT and DCT readings was not influenced by the thickness of the transplanted lamella. DISCUSSION The well-known difference in mean pressure readings between DCT and GAT was not affected by the increase in CCT following DSAEK. IOP readings with the GAT seem not to be influenced by the increase in CCT. Because of the remarkable differences in individual pairs of IOP measurements, both GAT and DCT should be used after DSAEK.

Predictability of Microkeratome-Dependent Flap Thickness for DSAEK

BACKGROUND The recommended thickness of the graft lamella in Descemets stripping automated endothelial keratoplasty (DSAEK) is 120 - 180 microm. To adjust for the large variation in central corneal thickness (CCT) of eye bank donor corneas, microkeratome plates of different heights are available. The aim of this study was to evaluate the lamella thickness predictability of different keratome plates in a clinical routine setting. METHODS In a prospective study of 60 consecutive DSAEK procedures, CCT was measured with a 50 MHz ultrasound pachymeter after meticulous epithelium removal immediately before and after lamella creation. Selected plate thickness was 300, 350, or 400 micro, respectively. Cutting depth was calculated by subtracting the remaining CCT of the deep lamella after the cut from the initial CCT before the cut. RESULTS The mean (+/- SD) cutting depth was 320 +/- 45 microm with the Amadeus 350 keratome, 317 +/- 48 microm with the Moria 300 keratome, 388 +/- 58 microm with the Moria 350 keratome and 467 +/- 94 microm with the Moria 400 keratome. Neither the duration nor the type of donor preservation had an effect on the accuracy of the cutting depth. CONCLUSION The mean cutting depth for the DSAEK keratomes is more accurate than the cutting depth of the same keratome heads designed for LASIK. This might be due to the fact that DSAEK lamellas were cut after complete epithelial removal. Despite the accurate mean cutting accuracy, there is a substantial variation between individual cuts which have to be taken into consideration.