Pavel Rozsíval

New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe

Background Chronic mucocutaneous candidiasis disease (CMCD) may result from various inborn errors of interleukin (IL)-17-mediated immunity. Twelve of the 13 causal mutations described to date affect the coiled-coil domain (CCD) of STAT1. Several mutations, including R274W in particular, are recurrent, but the underlying mechanism is unclear. Objective To investigate and describe nine patients with CMCD in Eastern and Central Europe, to assess the biochemical impact of STAT1 mutations, to determine cytokines in supernatants of Candida-exposed blood cells, to determine IL-17-producing T cell subsets and to determine STAT1 haplotypes in a family with the c.820C>T (R274W) mutation. Results The novel c.537C>A (N179K) STAT1 mutation was gain-of-function (GOF) for γ-activated factor (GAF)-dependent cellular responses. In a Russian patient, the cause of CMCD was the newly identified c.854 A>G (Q285R) STAT1 mutation, which was also GOF for GAF-dependent responses. The c.1154C>T (T385M) mutation affecting the DNA-binding domain (DBD) resulted in a gain of STAT1 phosphorylation in a Ukrainian patient. Impaired Candida-induced IL-17A and IL-22 secretion by leucocytes and lower levels of intracellular IL-17 and IL-22 production by T cells were found in several patients. Haplotype studies indicated that the c.820C>T (R274W) mutation was recurrent due to a hotspot rather than a founder effect. Severe clinical phenotypes, including intracranial aneurysm, are presented. Conclusions The c.537C>A and c.854A>G mutations affecting the CCD and the c.1154C>T mutation affecting the DBD of STAT1 are GOF. The c.820C>T mutation of STAT1 in patients with CMCD is recurrent due to a hotspot. Patients carrying GOF mutations of STAT1 may develop multiple intracranial aneurysms by hitherto unknown mechanisms.

LASIK for Myopia and Astigmatism Using the SCHWIND AMARIS Excimer Laser: An International Multicenter Trial

PURPOSE To assess the efficacy, predictability, and safety of LASIK for the surgical correction of low to moderate myopia with astigmatism using the SCHWIND AMARIS excimer laser. METHODS Six international study sites enrolled 358 eyes with a manifest refraction spherical equivalent (MRSE) from -0.50 to -7.38 diopters (D) (mean sphere: -3.13+/-1.58 D) with up to -5.00 D of astigmatism (mean: -0.69+/-0.67 D). All eyes underwent treatment with the nonwavefront-guided aspheric algorithm of the SCHWIND AMARIS excimer laser. All eyes were targeted for emmetropia. Refractive outcomes and corneal higher order aberrations were analyzed pre- and postoperatively. Visual quality was assessed using photopic and mesopic contrast sensitivity. Six-month postoperative outcomes are reported. RESULTS At 6 months postoperative, the MRSE for all eyes was -0.21+/-0.20 D, and 96% (343/358) of eyes had MRSE within +/-0.50 D. Uncorrected visual acuity was 20/20 or better in 98% (351/358) of eyes, and no eyes lost 2 or more lines of best spectacle-corrected visual acuity. The total corneal higher order aberrations root-mean-square increased by 0.09 microm, spherical aberration increased by 0.08 microm, and coma increased by 0.04 microm postoperatively. Photopic and mesopic contrast sensitivity did not change 6 months postoperatively. CONCLUSIONS Treatment of myopia with astigmatism using the SCHWIND AMARIS excimer laser is safe, efficacious, predictable, and maintains visual quality.

Penetrating keratoplasty for iatrogenic keratoconus after repeat myopic laser in situ keratomileusis: histologic findings and literature review.

&NA; We report a patient with a sufficiently thick cornea (593 &mgr;m) and no topographic signs of keratoconus preoperatively who developed iatrogenic keratoconus 2 months after repeat laser in situ keratomileusis (−4.00 −1.00 × 20) performed 5 months after the primary procedure (−10.50 −1.00 × 55). After penetrating keratoplasty, macrophotography showed severe multidirectional “macrostriae” of the stromal bed. On histologic evaluation, excessive thinning of the residual stromal bed to a minimum of 75 &mgr;m in the valleys and a maximum of 200 &mgr;m at the peaks of the macrostriae were documented. The flap thickness was 225 &mgr;m in the center. The thicker–than‐intended flap (160 &mgr;m) is thought to be the cause of the severe complication of the LASIK procedure.

Delayed-onset Pseudomonas stutzeri endophthalmitis after uncomplicated cataract surgery

Abstract An 88‐year‐old woman had uneventful extracapsular cataract extraction with posterior chamber intraocular lens (IOL) implantation her right eye. Seven weeks later, an anterior vitrectomy with removal of the IOL was performed because of endophthalmitis resistant to topical and systemic amoxicillin, cephalosporin, aminoglycoside, and steroids. Microbiological examination of the vitreous biopsy, capsule, and anterior chamber fluid disclosed Pseudomonas stutzeri gram‐negative nonfermentative bacteria sensitive to tetracycline, ceftazidime, gentamicin, ofloxacin, and piperacillin. Pseudomonas stutzeri should be considered in the treatment of delayed‐onset endophthalmitis.

Retreatment after photorefractive keratectomy for low myopia1,2

Abstract Objective The purpose of the study was to evaluate the results of retreatment for low myopia after primary photorefractive keratectomy (PRK). Design A prospective study. Participants A total of 48 eyes of 37 patients from 566 eyes of 331 patients originally treated for myopia of up to −6 diopters (D) were studied. Intervention Photorefractive keratectomy by the Coherent Schwind Keratom II excimer laser was performed. Main outcome measures The parameters evaluated were visual acuity, refraction, and corneal clarity. Results Of the 566 eyes with myopia up to −6 D, 48 eyes (8.5%) required retreatment. The sphere (mean ± standard deviation) was −0.88 ± 1.24 D before second surgery. At 6 months, the mean was −0.04 ± 0.91; at 1 year, it was −0.33 ± 0.75 D. At 6 months, 75% of sphere value was within ±1 D. The preoperative uncorrected visual acuity (UCVA) was 20/200 or worse in 12.8% of eyes and 20/40 or better in 40.4% of eyes. Six months after reoperation, 20/60 UCVA was obtained in 17.4% of eyes. All others (82.6%) had UCVA of 20/40 or better, 26.1% better than 20/20. The proportion of eyes with best spectacle-corrected visual acuity better than 20/20 decreased from 60.0% to 47.1% 6 months after reoperation. Six months after reoperation, haze 1 was present in 42.9% and haze 2 in 4.7% of eyes, and in no eye was haze worse. Conclusion Retreatment after PRK for low myopia can significantly increase UCVA and decrease residual refractive error without significant complications.

Phacoemulsification parameters: series 20000 Legacy Versus Legacy with AdvanTec software and NeoSoniX handpiece.

Purpose: To examine the differences in average phaco power and effective phaco time (EPT) and evaluate the clinical results with the standard Series 20000® Legacy® system (Alcon) and the Legacy with AdvanTec® software and the NeoSoniX® handpiece (Alcon). Setting: Department of Ophthalmology, University Hospital, Hradec Králové, Czech Republic. Methods: The mean phaco power and EPT in 240 eyes of 240 consecutive patients having cataract surgery by a single surgeon using the standard Legacy 20000 system were retrospectively compared with results in 240 eyes of 240 consecutive patients operated on by the same surgeon using the Legacy with AdvanTec software and the NeoSoniX handpiece. Statistical analysis was performed using the Kruskal‐Wallis 1‐way analysis of variance. All chi‐square (&khgr;2) values are approximations. Results: The EPT and mean phaco power were less in the AdvanTec–NeoSoniX group than in the standard Legacy 20000 group in all cases. The mean EPT was 56.9 seconds ± 29.5 (SD) in the standard Legacy 20000 group and 4.2 ± 3.8 seconds in the AdvanTec–NeoSoniX group. The mean phaco power was 19.2% ± 6.2% and 5.1% ± 2.5%, respectively. The difference between groups was statistically significant in EPT (age ≥90 years, &khgr;2 = 4.5, P = .034; age <90 years, &khgr;2>57, P<.00005) and in mean phaco power (&khgr;2 = 4.58 and P = .032 and &khgr;2>44 and P<.00005, respectively). No trace of corneal striae or edema was observed in 92% eyes on the first postoperative day. The best corrected visual acuity was 20/25 or better in 60% of cases. Conclusions: The Legacy system with AdvanTec software and the NeoSoniX handpiece significantly reduced the mean EPT and phaco power. This low‐power technology minimizes intraoperative damage to ocular structures and maximizes the level and rapidity of visual rehabilitation.

Rheohaemapheresis in the treatment of nonvascular age-related macular degeneration

PURPOSE To evaluate the experience with rheohaemapheresis (RH) in the treatment of age-related macular degeneration (AMD). METHODS Thirty-eight patients were each treated with 8 procedures of RH (14 males, 24 females). The control group consisted of 34 random patients (30 females, 4 males) with the dry form of AMD but not treated by RH. Our modification of the cascade method (named rheohaemapheresis) was used for plasma separation. After plasma separation (blood cell separator, Cobe Spectra, Denver, CO, USA), the separated plasma was pumped through a rheofilter (Evaflux 4A, Kuraray, Osaka, Japan) to remove lipoproteins and other high-molecular-weight rheologic factors. RESULTS In treated patients, best-corrected visual acuity (BCVA) increased significantly from 0.61 (0.06-1.00) to 0.68 (0.35-1.00) after 2.5 years (p = 0.035). We found no significant changes or differences in scotopic activity, whereas cone response and paramacular activity in the more peripheral region between 14° and 22° of eccentricity were significantly higher in treated patients after 2.5 years. CONCLUSION RH therapy favourably influenced BCVA. During 2.5 years after the therapy, no progression of dry to wet AMD was observed in our patients. RH reduced the area of drusenoid retinal pigment epithelium detachment (which increased during the natural course of dry form AMD). RH influenced rheological markers and probably improved metabolism in the affected retinal areas which lead to the aforementioned positive results.

Comparison of posterior capsule opacification after two different surgical methods of cataract extraction.

PURPOSE To compare the extent of posterior capsule opacification (PCO) after AquaLase and NeoSoniX phacoemulsification methods using two types of software for PCO quantification. DESIGN Prospective, randomized clinical trial. METHODS At the Department of Ophthalmology, University Hospital in Hradec Králové, 50 patients (100 eyes) were analyzed one year after surgery. AquaLase was used in the right eye and NeoSoniX in the left eye of each patient. One year after surgery, digital retroillumination photographs of anterior segments were obtained. The Evaluation of Posterior Capsule Opacification (EPCO) 2000 software (Berlin, Germany) and the Open-Access Systematic Capsule Assessment (OSCA) system (Edinburgh, United Kingdom) were used for PCO assessment. Best-corrected Snellen visual acuity (BCVA) was evaluated before and after surgery. Statistical analysis was performed using parametric tests. RESULTS The EPCO 2000 results were as follows: mean value for right eyes, 0.324+/-0.305; mean value for left eyes, 0.298+/-0.341; no difference was proved (P=.532). The OSCA results were as follows: for right eyes, 0.7097+/-0.3777; for left eyes, 0.8584+/-0.4323; significant difference (P=.046), worse for left eyes. No correlation between EPCO 2000 and OSCA results was established (P>.001; correlation coefficient, 0.347). BCVA for the right eyes was 0.837+/-0.262 and for the left eyes was 0.849+/-0.224. Neodymium:yytrium-aluminum-garnet capsulotomy was performed in one eye in the NeoSoniX group, and in no eyes in the AquaLase group. CONCLUSIONS There was no significant difference in PCO measured by EPCO 2000, however, PCO after AquaLase as assessed by EPCO 2000 was slightly denser. The OSCA system gave significantly higher scores in the NeoSoniX group. No correlation between EPCO 2000 and OSCA outcomes was proved.

Three-Year Follow-up of Posterior Capsule Opacification After AquaLase and NeoSoniX Phacoemulsification

PURPOSE To prospectively compare the degree of posterior capsule opacification (PCO) after AquaLase and NeoSoniX phacoemulsification methods during the 3-year follow-up period. DESIGN Prospective, randomized clinical trial. METHODS Setting at the Department of Ophthalmology, University Hospital in Hradec Králové. Patients with bilateral cataract were included. AquaLase was used in the right eye and NeoSoniX in the left eye of each patient. The AcrySof SA60AT intraocular lens (Alcon Laboratories, Fort Worth, Texas, USA) was implanted in all eyes. The Evaluation of Posterior Capsule Opacification (EPCO) 2000 software (Developed by Tetz MR and associates, Berlin, Germany) and the Open-Access Systematic Capsule Assessment (OSCA) system (Devised by Aslam TM, Edinburgh, United Kingdom) were used for PCO assessment 1, 2, and 3 years after cataract surgery. RESULTS Fifty patients were analyzed 1 year, 47 patients 2 years, and 46 patients 3 years after cataract surgery. Mean EPCO 2000 values were for the AquaLase group 0.324 +/- 0.305 and for the NeoSoniX group 0.298 +/- 0.341 (P = .53) 1 year after surgery, for the AquaLase group 0.429 +/- 0.322 and for the NeoSoniX group 0.478 +/- 0.337 (P = .30) 2 years after surgery, and for the AquaLase group 0.582 +/- 0.506 and for the NeoSoniX group 0.594 +/- 0.515 (P = .87) 3 years after surgery. The OSCA results were for the AquaLase group 0.7097 +/- 0.3778 and for the NeoSoniX group 0.8584 +/- 0.4323 (P = .046) 1 year after surgery, for the AquaLase group 0.7515 +/- 0.4555 and for the NeoSoniX group 0.8103 +/- 0.4498 (P = .44) 2 years after surgery, and for the AquaLase group 0.9667 +/- 0.736 and for the NeoSoniX group 0.9540 +/- 0.5250 (P = .91) 3 years after surgery. Neodymium-yttrium-aluminun-garnet capsulotomy rate for AquaLase vs NeoSoniX was 0:1 eyes 1 year, 1:3 eyes 2 years, and 1:4 eyes 3 years after surgery. No significant difference between those 2 groups was established, except the OSCA outcomes 1 year postoperatively. CONCLUSION There was only minimal PCO difference between these 2 approaches, AquaLase and NeoSoniX. Neither AquaLase nor NeoSoniX technique was able to prevent a natural progression of PCO.

Comparison of the effect of AquaLase and NeoSoniX phacoemulsification on the corneal endothelium

PURPOSE: To compare the extent of corneal endothelial cell loss and pachymetry changes in 2 age‐based groups of patients who had cataract removal by AquaLase (Alcon) phacoemulsification in 1 eye and NeoSoniX (Alcon) phacoemulsification in the contralateral eye. SETTING: Department of Ophthalmology, University Hospital, Hradec Králové, Czech Republic. METHODS: This prospective clinical study comprised 28 patients younger than 80 years (Group A) and 28 patients 80 years or older (Group B) with bilateral cataract having lens removal using AquaLase in the right eye and NeoSoniX in the left eye. The nuclei were graded clinically on the basis of hardness. The endothelial cell count (ECC), pachymetry, and best corrected visual acuity (BCVA) were evaluated preoperatively and postoperatively. The mean ECC and pachymetry values (±SD) were calculated in each group, with differences between right and left eyes analyzed using the paired t test. RESULTS: In Group A, the differences in the postoperative changes in ECC and pachymetry between AquaLase and NeoSoniX were not statistically significant. In Group B, there were statistically significant differences in postoperative changes in ECC and pachymetry, with the results better in the AquaLase eyes. The BCVA immediately after surgery was better than preoperatively in all eyes. CONCLUSION: The results suggest that AquaLase cataract extraction is safe for the endothelium, even in older patients with harder cataracts and a lower ECC count preoperatively.