Loss-of-function variants in UBAP1L cause autosomal recessive retinal degeneration.

PURPOSE: Inherited retinal diseases (IRDs) are a group of monogenic conditions that can lead to progressive blindness. Their missing heritability is still considerable, due in part to the presence of disease genes that await molecular identification. The purpose of this work was to identify novel genetic associations with IRDs. METHODS: Patients underwent a comprehensive ophthalmological evaluation using standard-of-care tests, such as detailed retinal imaging (macular optical coherence tomography and short-wavelength fundus autofluorescence) and electrophysiological testing. Exome and genome sequencing, as well as computer-assisted data analysis were used for genotyping and detection of DNA variants. A minigene-driven splicing assay was performed to validate the deleterious effects of 1 of such variants. RESULTS: We identified 8 unrelated families from Hungary, the United States, Israel, and The Netherlands with members presenting with a form of autosomal recessive and nonsyndromic retinal degeneration, predominantly described as rod-cone dystrophy but also including cases of cone/cone-rod dystrophy. Age of disease onset was very variable, with some patients experiencing first symptoms during their fourth decade of life or later. Myopia greater than 5 diopters was present in 5 of 7 cases with available refractive data, and retinal detachment was reported in 2 cases. All ascertained patients carried biallelic loss-of-function variants in UBAP1L (HGNC: 40028), a gene with unknown function and with homologies to UBAP1, encoding a protein involved in ubiquitin metabolism. One of these pathogenic variants, the intronic NM_001163692.2:c.910-7G>A substitution, was identified in 5 unrelated families. Minigene-driven splicing assays in HEK293T cells confirmed that this DNA change is responsible for the creation of a new acceptor splice site, resulting in aberrant splicing. CONCLUSION: We identified UBAP1L as a novel IRD gene. Although its function is currently unknown, UBAP1L is almost exclusively expressed in photoreceptors and the retinal pigment epithelium, hence possibly explaining the link between pathogenic variants in this gene and an ocular phenotype.

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration.

PURPOSE: To detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept. PATIENTS AND METHODS: Twenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 µl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system. RESULTS: A significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 µg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 µg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 µg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95). CONCLUSION: According to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Atrophy of retinal vessels in neovascular age-related macular degeneration following long-term treatment with 20 intravitreal anti-VEGF injections.

BACKGROUND: The study aimed to evaluate the changes in retinal vascular density in exudative age-related macular degeneration (AMD) after long-term anti-VEGF treatment using optical coherence tomography angiography (OCT-A), and to compare these changes with the vascular density in AMD treated for one year and healthy eyes. METHODS: In our cross-sectional study OCT-A was performed on 60 eyes of 60 patients. Group AMD 20 × consisted of patients receiving long-term (minimum 20 injections) aflibercept therapy (n = 17), and Group AMD one year consisted of patients treated for one year with a treat & extend protocol (n = 25). The vascular density values obtained with OCT-A were compared with an age-matched control group of 18 healthy eyes. We examined the central retinal thickness (CRT), the vascular density of the fovea and parafovea in the superficial and deep retinal plexus, and evaluated the extent of the non-flow area and the foveal avascular zone (FAZ) on a 3 × 3 mm macular region. Kruskal-Wallis test was performed for statistical analysis. RESULTS: In Group AMD 20x, the vascular density of superficial retinal plexus in the fovea (p = 0.0022) and parafovea (p < 0.0001) was significantly lower compared to Group one year and control group. In the deep retinal plexus, vascular density in the fovea (p = 0.0033) was significantly lower in both AMD groups compared to the control group, with no difference in the parafoveal region (p = 0.0774). The extent of non-flow area (p = 0.0003) and FAZ (p = 0.0008) were significantly larger in both AMD groups compared to the control group. There was a significant difference in CRT between those treated for one year and control eyes (p = 0.0036). CONCLUSIONS: In our study, we demonstrated that macular vessel density was lower in the foveal area in the superficial retinal plexus in AMD patients after one year and long-term anti-VEGF treatment. These vascular density changes were absent in the parafoveal and whole areas of the deep retinal plexus. Our results indicate that long-term anti-VEGF treatment reduces the vascular density of the superficial retinal plexus to a greater extent compared to the deep retinal plexus.

Evaluation of the mechanical properties of the anterior lens capsule following femtosecond laser capsulotomy at different pulse energy settings.

PURPOSE: To evaluate and compare the mechanical properties of anterior capsule opening performed with femtosecond laser capsulotomy at different energy settings in ex vivo porcine anterior lens capsule specimens. METHODS: Twenty-five fresh porcine eyes per group were included in the study. Femtosecond laser capsulotomy was performed with three different pulse energy levels: 2 µJ (low energy group), 5 µJ (intermediate energy group), and 10 µJ (high energy group). The capsule openings were stretched with universal testing equipment until they ruptured. The morphologic profile of the cut capsule edges was evaluated using scanning electron microscopy. RESULTS: The high energy group had significantly lower rupture force (108 ± 14 mN) compared to the intermediate energy group (118 ± 10 mN) (P < .05) and low energy group (119 ± 11 mN) (P < .05), but the difference between the intermediate energy and low energy groups was not significant (P = .9479). The high energy group had significantly lower circumference stretching ratio (144% ± 3%) compared to the intermediate energy group (148% ± 3%) (P < .05) and low energy group (148% ± 3%) (P < .05), but the difference between the intermediate energy group and low energy group was not significant (P = .9985). Scanning electron microscopy images showed that the edge was only serrated with low and intermediate energy, but additional signs of collagen melting and denaturation were observed at high energy. CONCLUSIONS: Anterior capsule openings created at a high energy level were slightly weaker and less extensible than those created at low or intermediate levels, possibly due to the increased thermal effect of photo-disruption.

The use of femtosecond lasers in cataract surgery: review of the published results with the LenSx system.

PURPOSE: To review the published literature describing the use of the LenSx femtosecond laser technology (Alcon Laboratories, Inc., Fort Worth, TX) in cataract surgery. METHODS: Literature review. RESULTS: The LenSx system has been used in more than 200,000 cataract surgery procedures to date. Pre-clinical evaluations have shown that this system produces accurate and reproducible capsulorhexes, and that both the energy required for phacoemulsification and total phacoemulsification time are less than with conventional phacoemulsification. In comparative studies, femtosecond lasers have been shown to produce more precise and reproducible capsulorhexes than manual procedures, and better intraocular lens placement; capsule overlap, circularity of capsulotomy, and centration of the intraocular lens are consistently better with femtosecond lasers than with manual procedures. The improved quality of capsulorhexis and intraocular lens positioning are reflected in favorable visual and refractive outcomes. As with any new technology, there is a significant learning curve: prospective cohort studies have shown that the incidence of intraoperative complications such as suction breaks or anterior capsular tears or tags decreases with experience. In general, the incidence of such complications is within the range (< 2%) considered in recent evidence-based guidelines to be feasible and desirable. CONCLUSIONS: Although femtosecond laser cataract surgery is in its infancy, the technology is evolving rapidly and offers the potential for more consistent and predictable results after cataract surgery.

Evaluation of femtosecond laser-assisted and manual clear corneal incisions and their effect on surgically induced astigmatism and higher-order aberrations.

PURPOSE: To evaluate femtosecond laser-assisted and manual clear corneal incisions and their effect on surgically induced astigmatism (SIA) and corneal higher-order aberrations (HOAs). METHODS: In a prospective randomized study, conventional phacoemulsification with a 2.8-mm clear corneal incision using a disposable keratome was performed in 20 eyes of 20 patients (manual group), and femtosecond laser-assisted cataract surgery with a 2.8-mm biplanar clear corneal tunnel created by a femtosecond laser (LenSx; Alcon Laboratories, Inc., Aliso Viejo, CA) was performed in 20 eyes of 20 patients (femtosecond laser group). Corneal topography readings and corneal wavefront aberrations (diameter: 9.0 mm) were obtained using a Scheimpflug camera (Pentacam HR; Oculus Optikgerate, Wetzlar, Germany) preoperatively and 3 months postoperatively. RESULTS: There was no significant difference in SIA between the groups (femtosecond laser group: 0.47 ± 0.13 vs manual group: 0.41 ± 0.14; P = .218), but the axis deviation of the SIA axis from the previously planned axis was significantly smaller in the femtosecond laser group compared to the manual group (4.47°± 2.59° vs 7.38°± 4.72°, respectively; P = .048). Corneal HOAs increased significantly in both groups (femtosecond laser group: 0.13 ± 0.09 to 0.18 ± 0.12, P = .025; manual group: 0.13 ± 0.05 to 0.15 ± 0.05, P = .002), but preoperative and postoperative values did not differ significantly between them (P = .472 and .078, respectively). Lower-order and total corneal aberration values remained stable in both groups (P > .05). CONCLUSIONS: There was no difference in SIA and induced HOAs between manual and femtosecond laser-created clear corneal incisions.

The effect of femtosecond laser capsulotomy on the development of posterior capsule opacification.

PURPOSE: To evaluate and compare the effects of femtosecond laser-assisted anterior capsulotomy and manual anterior capsulorhexis on posterior capsule opacification (PCO) development. METHODS: Femtosecond laser-assisted anterior capsulotomy was performed in 40 eyes of 40 patients (FS group) and manual anterior capsulorhexis was performed in 39 eyes of 39 patients (CCC group). An AcrySof one-piece hydrophobic acrylic intraocular lens (Alcon Laboratories, Inc., Fort Worth, TX) was implanted in all eyes. The PCO level was measured using Open-Access Systematic Capsule Assessment (OSCA) software 18 to 26 months after surgery. Postoperative intraocular lens position (ie, tilt and decentration) was measured using Scheimpflug images (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany). RESULTS: There was no statistically significant difference in age, axial length, and follow-up time between the two groups (P > .05). Vertical tilt, horizontal and total decentration of intraocular lenses, and PCO proved to be significantly higher in the CCC group (P = .03, .04, .03, and .01, respectively). After adjusting for axial length and follow-up time, manual anterior capsulorhexis was found to be a significant predictor of higher PCO scores in the multivariable regression model (ß: 0.33; 95% CI: 0.01 to 0.65; P = .04). Vertical tilt affected PCO scores after adjusting for axial length and follow-up time (ß: 0.07; 95% CI: 0.01 to 0.12; P = .02). No capsulotomies were performed during follow-up in either group. CONCLUSIONS: Femtosecond laser-assisted anterior capsulotomy proved to be a safe procedure for postoperative PCO rates. Due to better intraocular lens position, femtosecond laser-assisted anterior capsulotomy resulted in slightly decreased PCO scores; however, evaluating its clinical significance requires further studies.

Comparison of the mechanical properties of the anterior lens capsule following manual capsulorhexis and femtosecond laser capsulotomy.

PURPOSE: To evaluate and compare the mechanical properties of anterior capsule openings performed with the continuous curvilinear capsulorhexis (CCC) technique and femtosecond laser capsulotomy (FLC) in ex vivo porcine lens capsule specimens. METHODS: Fresh porcine eyes were included in the study (CCC group, n = 50; FLC group, n = 30). The capsule openings were stretched with universal testing equipment until they ruptured. The rupture force and circumference stretching ratio were evaluated. The morphologic profile of the cut capsule edges was evaluated using scanning electron microscopy (SEM). RESULTS: The average rupture force was higher in the CCC group (median: 155 mN; interquartile range [IQR]: 129 to 201 mN; range: 71 to 294 mN) than in the FLC group (median: 119 mN; IQR: 108 to 128 mN; range: 91 to 142 mN) (P < .01, Mann-Whitney U test). The average circumference stretching ratio in the CCC group was greater (median: 150%; IQR: 146% to 156%; range: 136% to 161%) than in the FLC group (median: 148%; IQR: 145% to 150%; range: 141% to 154%) (P = .0468, Mann-Whitney U test). When less than 71 mN, no capsular tear occurred in either group. When less than 91 mN, no capsular tear occurred in the FLC group, whereas at 91 mN, the probability of capsular tears was 9% for the CCC group. SEM examination found that the CCC group had smooth edges, whereas those of the FLC group were gently serrated. CONCLUSIONS: According to the current results in a porcine eye model, FLC had less average resistance to capsule tear than CCC, but the weakest openings were seen in the CCC group.

Femtosecond laser cataract incision morphology and corneal higher-order aberration analysis.

PURPOSE: Analysis of the femtosecond laser refractive lens surgery corneal incision configuration and corneal higher-order aberration (HOA) effect from the first postoperative day. METHODS: High-resolution anterior segment optical coherence tomography was used to assess 20 eyes undergoing femtosecond laser refractive lens surgery with 2.2-mm minimal incision. The primary incision (tri-planar) actual length, cord length, surface angle, surface irregularity, and regional pachymetry values and the secondary incision (uni-planar) length, angle, surface irregularity, and pachymetry values were analyzed. Hartmann-Shack aberrometer was used to assess corneal HOAs to correlate the effect. Assessment was done preoperatively and 1 month postoperatively. RESULTS: The actual length, cord length, and surface angle means for the primary incision in the first postoperative day and month were 1.50 ± 0.1 and 1.47 ± 0.2 mm (P = .5), 1.41 ± 0.1 and 1.42 ± 0.2 mm (P = .8), and 27° ± 4° and 23° ± 5° (P = .07), respectively. The length and surface angle for the secondary incision in the first postoperative day and month were 1.17 ± 0.01 and 1.04 ± 0.1 mm (P = .05) and 52° ± 3° and 42° ± 5° (P = .007). The regional pachymetry values for the primary and secondary incisions were significantly increased in the first postoperative day and then significantly decreased after 1 month. All irregularities occurred in the posterior surface (endothelium): 2 cases of posterior gap (first day) and 1 case of posterior retraction (first month). The HOAs had not significantly changed preoperatively and after 1 month. CONCLUSIONS: The femtosecond laser refractive lens surgery incision is stable and does not significantly change the HOA.

Anterior segment OCT imaging after femtosecond laser cataract surgery.

PURPOSE: To report the anterior segment imaging characteristics after femtosecond laser assisted cataract surgery. METHODS: Cataract surgery was performed with the LenSx femtosecond laser (Alcon-LenSx Inc., Aliso Viejo, CA) in 40 eyes of 40 patients. The laser was programmed to perform a 4.5-mm capsulorhexis, a cross-pattern fragmentation of the nucleus, a 2.8-mm main incision, and a 1.0-mm side-port incision. The anterior segment was then analyzed using the Visante OCT anterior segment program (Zeiss-Meditec AG, Jena, Germany). RESULTS: The preoperatively set treatment parameters correlated well with the achieved results. For the capsulorhexis, the femtosecond laser cut was programmed to start 350 µm behind the anterior lens capsule and OCT measured 377 ± 55.3 µm. Nucleus fragmentation was programmed to start 750 µm in front of the posterior capsule and end 550 µm behind the anterior capsule, and OCT measured 794 ± 111 and 568 ± 147 µm, respectively. The diameter of the capsulorhexis measured by OCT was 4.54 ± 0.2 mm, compared to the 4.5 mm programmed. CONCLUSIONS: Anterior segment OCT imaging was able to detect the tissue changes within the lens after femtosecond laser capsulorhexis and nucleus fragmentation. The measured values correlated well with the planned treatment parameters.

First-in-Human Safety Study of Femtosecond Laser Image-Guided Trabeculotomy for Glaucoma Treatment: 24-month Outcomes.

Purpose: Pilot study to evaluate adverse events and intraocular pressure (IOP)-lowering of a novel, noninvasive glaucoma procedure, femtosecond laser, image-guided, high-precision trabeculotomy (FLIGHT). Design: Prospective, nonrandomized, single-center, interventional, single-arm clinical trial. Participants: Eighteen eyes from 12 patients with open-angle glaucoma. Methods: Eighteen eyes from 12 patients underwent FLIGHT, creating a single channel measuring 500-µm wide by 200-µm high through the trabecular meshwork and into Schlemm's canal. Adverse events, IOP, and other parameters were evaluated out to 24 months. Main Outcome Measures: Outcomes were the rates and types of adverse events and the rate of postprocedure best-corrected visual acuity loss (≥ 2 lines) compared with baseline. Efficacy outcomes were reduction in mean intraocular pressure (IOP) with respect to baseline and the percentage of eyes with a ≥ 20% reduction in IOP. Results: Eighteen eyes from 12 patients were enrolled in the study; 11 patients (17 eyes) returned at 24 months. There were no serious adverse events related to the laser treatment. Well-defined channels were clearly visible at 24 months by gonioscopy and anterior segment OCT, with no evidence of closure. At 24 months, the mean IOP was reduced by 34.6% from 22.3 ± 5.5 to 14.5 ± 2.6 mmHg (P < 5e-5), with an average of 2.0 ± 1.2 hypotensive medications compared with 2.2 ± 1.1 at baseline (P = 0.22). Fourteen out of the 17 study eyes (82.3%) achieved a ≥ 20% reduction in IOP at 24 months when compared with baseline. Conclusion: The FLIGHT system demonstrated a favorable safety profile in this initial pilot study, with no device-related serious adverse events. The channels appeared patent at 24 months, indicating medium-term durability. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Ophthalmic Aspects of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: A Narrative Review.

The aim of our review article was to summarize the current literature on Stevens-Johnson syndrome (SJS) and its severe form, toxic epidermal necrolysis (TEN). SJS/TEN is a serious, rare multi-system, immune-mediated, mucocutaneous disease with a significant mortality rate that can lead to severe ocular surface sequelae and even to bilateral blindness. Restoration of the ocular surface in acute and chronic SJS/TEN is challenging. There are only limited local or systemic treatment options for SJS/TEN. Early diagnosis, timely amniotic membrane transplantation and aggressive topical management in acute SJS/TEN are necessary to prevent long-term, chronic ocular complications. Although the primary aim of acute care is to save the life of the patient, ophthalmologists should regularly examine patients already in the acute phase, which should also be followed by systematic ophthalmic examination in the chronic phase. Herein, we summarize actual knowledge on the epidemiology, aetiology, pathology, clinical appearance and treatment of SJS/TEN.

Qualitative and quantitative comparison of two semi-manual retinal vascular density analyzing methods on optical coherence tomography angiography images of healthy individuals.

The aim of this study was to evaluate qualitative and quantitative differences in vascular density analysis of an established and a novel alternative for post-processing on optical coherence tomography angiography (OCTA) images in healthy individuals. OCTA examinations of 38 subjects were performed. After extracting the images, two semi-manual post-processing techniques, the already established Mexican hat filtering (MHF) and an alternative, the Shanbhag thresholding (ST) were applied. We assessed Vessel Density (VD), Skeleton Density (SkD) and Vessel Diameter Index (VDI). We analyzed the results in order to establish similarities or potentially relevant differences. Regarding SkD and VD, MHF generally gave higher values than ST. Simultaneously, mean values were also predominantly higher by MHF; however, standard deviations (SD) were higher by ST (range [mean ± SD]: 0.054 ± 0.038 to 0.134 ± 0.01 and 0.134 ± 0.095 to 0.362 ± 0.028 vs 0.012 ± 0.014 to 0.087 ± 0.03 and 0.039 ± 0.047 to 0.4 ± 0.095 for SkD and VD with MHF vs SkD and VD with ST, respectively). Values of VDI were considerably higher with ST than with MHF, while standard deviation was still significantly higher with ST (range [mean ± SD]: 2.459 ± 0.144 to 2.71 ± 0.084 and 2.983 ± 0.929 to 5.19 ± 1.064 for VDI with MHF and ST, respectively). The noise level reduction of the two methods were almost identical (noise levels: 65.8% with MHT and 65.24% with ST). Using MHF, the vascular network gets more fragmented by an average of 40% compared to ST. Both methods allow the segmentation of the vascular network and the examination of vascular density parameters, but they produce largely inconsistent results. To determine if these inconsistent results are clinically meaningful, and which method is more suitable for clinical use, our results provide further evidence that detailed understanding of the image analysis method is essential for reliable decision making for patients with retinal pathology. For longitudinal monitoring, use of the same image processing method is recommended.

Comparison of IOL power calculation and refractive outcome after laser refractive cataract surgery with a femtosecond laser versus conventional phacoemulsification.

PURPOSE: To compare intraocular lens (IOL) power calculation and refractive outcome between patients who underwent laser refractive cataract surgery with a femtosecond laser and those with conventional cataract surgery. METHODS: In this prospective study, 77 eyes from 77 patients underwent laser refractive cataract surgery (laser group; Alcon LenSx femtosecond laser), and conventional cataract surgery with phacoemulsification was performed in 57 eyes from 57 patients (conventional group). Biometry was done with optical low coherence reflectometry (Lenstar LS900, Haag-Streit AG), and IOL calculation was performed with third-generation IOL formulas (SRK/T, Hoffer Q, and Holladay). The refractive outcome was analyzed using the mean absolute error (MAE; difference between predicted and achieved postoperative spherical equivalent refraction), and multivariable regression analysis was performed to compare the two groups. RESULTS: No significant differences were found between age, axial length, keratometry, and preoperative corrected visual acuity in the laser and conventional groups (P>.05; Mann-Whitney U test). At least 6 weeks after surgery, MAE was significantly lower in the laser group (0.38±0.28 diopters [D]) than in the conventional group (0.50±0.38 D) (P=.04). The difference was the greatest in short (axial length <22.0 mm, 0.43±0.41 vs 0.63±0.48) and long (axial length >26.0 mm, 0.33±0.24 vs 0.63±0.42) eyes. CONCLUSIONS: Laser refractive cataract surgery with a femtosecond laser resulted in a significantly better predictability of IOL power calculation than conventional phacoemulsification surgery. This difference is possibly due to a more precise capsulorrhexis, resulting in a more stable IOL position.

Comparison of long-term visual outcome and IOL position with a single-optic accommodating IOL After 5.5- or 6.0-mm Femtosecond laser capsulotomy.

PURPOSE: To evaluate the long-term visual outcome and intraocular (IOL) position parameters with a single-optic accommodating IOL after 5.5- or 6.0-mm femtosecond laser capsulotomy. METHODS: This prospective, randomized, pilot study comprised 17 eyes from 11 patients (7 men) with a mean age of 65.82±10.64 years (range: 51 to 79 years). All patients received a Crystalens AT-50AO (Bausch & Lomb) accommodating IOL after femtosecond laser refractive cataract surgery using either a 5.5-mm capsulotomy (5.5-mm group; 9 eyes) or 6.0-mm capsulotomy (6.0-mm group; 8 eyes). Near and distance visual acuities, manifest refraction spherical equivalent (MRSE), and IOL tilt and decentration were evaluated 1 year postoperatively. RESULTS: No significant differences were noted between groups for postoperative uncorrected distance visual acuity, uncorrected near visual acuity, distance-corrected near visual acuity, and MRSE. Vertical and horizontal tilt were significantly higher in the 6.0-mm group than in the 5.5-mm group (P=.014 and P=.015, respectively). No significant difference was observed between groups regarding IOL decentration. CONCLUSIONS: A 5.5-mm capsulotomy created with a femtosecond laser is associated with less IOL tilt and therefore may be superior to a 6.0-mm capsulotomy when implanting a single-optic accommodating IOL.

Central corneal volume and endothelial cell count following femtosecond laser-assisted refractive cataract surgery compared to conventional phacoemulsification.

PURPOSE: To compare the effect of conventional phacoemulsification and femtosecond laser-assisted cataract surgery on the cornea using Scheimpflug imaging and noncontact specular microscopy. METHODS: In each group, 38 eyes (38 patients) underwent cataract surgery using either femtosecond laser-assisted (Alcon LenSx laser) (femtolaser group) or conventional phacoemulsification (phaco group). Central corneal thickness, 3-mm corneal volume, and Pentacam Nucleus Staging (PNS) were determined by a rotating Scheimpflug camera (Pentacam HR, Oculus Optikgeräte GmbH), and the volume stress index was calculated at 1 day and 1 month postoperatively. Endothelial cell count was measured by noncontact specular microscopy preoperatively, 1 day, 1 week, and 1 month postoperatively. RESULTS: Central corneal thickness was significantly higher in the phaco group (607±91 µm) than in the femtolaser group (580±42 µm) on day 1, but did not differ significantly preoperatively and at 1 week and 1 month. Volume stress index at day 1 was significantly lower in the femtolaser group than in the phaco group (P<.05) but did not differ significantly at 1 month. Multivariate regression analysis showed that the type of surgery had a significant effect on central corneal thickness. CONCLUSIONS: Femtosecond laser-assisted cataract surgery causes less corneal swelling in the early postoperative period and may cause less trauma to corneal endothelial cells than manual phacoemulsification.

Intraocular lens tilt and decentration measured by Scheimpflug camera following manual or femtosecond laser-created continuous circular capsulotomy.

PURPOSE: To compare intraocular lens (IOL) decentration and tilt following a circular capsulotomy created with a femtosecond laser (laser CCC) to a manually performed continuous curvilinear capsulorrhexis (manual CCC). METHODS: In a prospective, randomized study, a laser CCC (Alcon LenSx Inc) was performed in 20 eyes from 20 patients and a manual CCC was performed in 25 eyes from 25 patients. Intraocular lens decentration and tilt were measured using a Scheimpflug camera (Pentacam, Oculus Optikgeräte GmbH) 1 year after surgery. Uncorrected (UDVA) and corrected distance visual acuity (CDVA) and manifest refraction were also determined postoperatively. Between-group differences of IOL decentration and tilt as well as the correlation between IOL decentration and postoperative refractive changes and between IOL tilt and visual acuity were analyzed. RESULTS: Horizontal and vertical tilt were significantly higher in the manual CCC group (P=.007 and P<.001, respectively). Lenses implanted after manual CCC showed greater horizontal and total decentration (P=.034 and P=.022, respectively). Significant differences were found in the homogeneity of dichotomized IOL vertical tilt and both horizontal and total decentration distribution (P=.008, P=.036, and P=.017, respectively). Total IOL decentration showed a significant correlation with changes in manifest refraction values between 1 month and 1 year after surgery (R=0.33, P=.032). A significant correlation was noted between IOL vertical tilt and CDVA (R(2)=0.17, ß=-0.41, 95% confidence limit: -0.69 to -0.13, P=.005). CONCLUSIONS: Continuous curvilinear capsulorrhexis created with a femtosecond laser resulted in a more stable refractive result and less IOL tilt and decentration than manual CCC.

The role of femtolaser in cataract surgery.

Having been very successful in corneal surgery, femtolasers were recently introduced into the surgery of crystalline lens. The most important indications and advantages include: perfectly centered and sized capsulotomy, liquefaction of softer lenses and fragmentation of harder lenses which allows for chopping the nucleus without the use of phaco energy. Femtolaser can also be used for creating corneal wounds (tunnels) of any size at any location, and in order to manage the preoperative astigmatism using arcuate incisions at the desired depth within the cornea. Because of controlled steps in cataract surgery, wide acceptance and spread is to be expected.

Novel Meibomian Gland and Tarsal Conjunctival Changes Associated with Trastuzumab, Pertuzumab, and Anastrozole Treatment for Metastatic HER2 Positive Breast Cancer: A Case Report and Literature Review.

The aim of the study was to report a case of severe meibomian gland dysfunction (MGD) and conjunctival changes associated with trastuzumab, pertuzumab, and anastrozole therapy in a HER-2 positive breast cancer patient. A 57-year-old white woman was treated with trastuzumab and pertuzumab biological and anastrozole endocrine therapy for metastatic breast cancer for several months. She suffered from intense eye pain and foreign body sensation. On the ocular surface, severe MGD developed without corneal lesions. On the tarsal conjunctiva, circumscribed lesions evolved 6 months after receiving anticancer therapy. After biopsy, the histological assessment excluded metastasis or chalazion. The lesion consisted of subepithelial lymphocytic infiltrates surrounding lipid-laden CD68-positive macrophages. Besides the redundant lipid accumulation, no acute necrotic reaction was seen. Noncontact infrared meibography visualized ductal drop-out in the upper and lower lids, and functional tests confirmed severe MGD. During the 18-month follow-up, the patient received treatment for MGD and no new conjunctival lesions developed, subjective symptoms subsided, and ocular surface morphology remained unchanged. The novel HER2-inhibitor trastuzumab and pertuzumab biological therapy and anastrozole endocrine therapy were associated with the disruption of the ocular surface milieu. The new histological aspect of tarsal conjunctiva changes may give a hint to understand the potential underlying molecular mechanisms of anticancer therapy-associated severe MGD. Since anticancer therapies may substantially interfere with the ocular surface milieu, awareness of this side effect leads to improved care of oncology patients.

Corneal density with the Pentacam after photorefractive keratectomy.

PURPOSE: To measure corneal density and evaluate corneal haze in unoperated eyes and in eyes after photorefractive keratectomy (PRK). METHODS: Forty-nine patients (91 eyes) who underwent PRK and 48 control patients (76 unoperated eyes) were measured with the densitometry program of the Pentacam Scheimpflug imaging system (Oculus Optikgeräte GmbH) (0=no clouding, 100=tissue completely opaque). Eyes were categorized as myopic or hyperopic (myopia group and hyperopia group), with subgroups defined as unoperated (unoperated myopia group and unoperated hyperopia group), postoperative clear corneas (clear cornea myopia group and clear cornea hyperopia group), and postoperative with haze (myopia haze group and hyperopia haze group). The ANOVA option of the Statistica 8.1 program package (StatSoft Inc) was used to compare subgroups. RESULTS: Maximum density of postoperative corneas with haze (myopia haze group, 46.2±16.2; hyperopia haze group, 50.2±25.8) was higher than in postoperative clear corneas (clear cornea myopia group, 29.9±8.7; clear cornea hyperopia group, 22.9±3.1), but maximum corneal density in the latter subgroups showed no difference compared with unoperated controls (unoperated myopia group, 25.1±2.4; unoperated hyperopia group, 22.8±3.2). Differences among subgroups were not found outside the 6-mm diameter ablation zone. In hazy myopic corneas, there was a strong decreasing density trend from the apex to the 3-mm radius (P<.001, R=-0.5), which continued towards the periphery at 4.5 mm (P=.019, R=-0.21). Hyperopic mild hazy corneas showed a density increase from the apex to 3 mm (P<.001, R=0.4), followed by a decrease towards the periphery (P<.01, R=-0.4). CONCLUSIONS: The densitometry program of the Pentacam can provide a useful objective measure of postoperative and other mild corneal haze.