12-year follow-up of the first endothelial keratoplasty without Descemet stripping in a 3-month newborn with Congenital Hereditary Endothelial Dystrophy (CHED).

BACKGROUND: Endothelial Keratoplasty (EK) is now considered as the standard treatment for Congenital Hereditary Endothelial Dystrophy (CHED) by many surgeons. We present the 12-year clinical outcome of the youngest operated patient with CHED in which we successfully performed a bilateral EK procedure without removing the recipient endothelium-Descemet complex. CASE PRESENTATION: In November 2010 we performed EK without Descemet Stripping in a 3-month female newborn, thinking that the lower manipulation obtained by leaving the recipient endothelium-Descemet complex could be the key factor for the success of our surgery. Such a particular technique was new in newborns. The surgery was a success, but the long-term visual result was not predictable at that time. We followed the patient at 4 months, and then yearly. At the latest visit in October 2022 the visual, cognitive, and motorial developments were normal, with Best-corrected Distance Visual Acuity of 0.4 LogMAR with - 0.75 D sf + 2.75 D cyl @ 105° in the right eye (RE) and 0.4 LogMAR with + 1.50 D sf + 2.50 D cyl @ 60° in the left eye (LE). The endothelial microscope showed an unexpected healthy endothelium, with a cell count of 2383 cells/mm2 in the RE and of 2547 cells/mm2 in the LE from a starting donor count of 2900 cells/mm2. No secondary procedures were performed during the 12-year follow-up. CONCLUSION: EK without Descemet stripping has proved to be a successful procedure over time in our newborn. The unexpected healthy endothelium suggests a role of the Descemet membrane in CHED.

Posterior capsule dynamics during femtosecond laser lens fragmentation.

PURPOSE: The dynamics of the posterior capsule during femtosecond laser lens fragmentation has received little attention in the literature. We analysed the movements of the posterior capsule to identify the rupture risk factors, if any, and to suggest possible modification of the laser spot energy pattern during fragmentation. MATERIALS AND METHODS: Posterior capsule ruptures during fragmentation were identified over a 10-year period of femtosecond laser use. In addition, the dynamics of the posterior capsule were identified through the real-time swept-source OCT lateral view available during the surgeries. RESULTS: Out of the 1465 laser cataract procedures performed, we recorded 1 case of posterior capsule rupture during lens fragmentation, which was caused by eye movement that was detected but ignored by the surgeon. Three types of posterior capsule dynamics were identified, all related to a gas bubble formation during the first part of the lens fragmentation. In eyes with a hard nucleus, the concussion of the posterior capsule was evident, however, with no capsule rupture. DISCUSSION: Maintaining good docking throughout the whole procedure seems important in avoiding a posterior capsule cut by the femtosecond laser. In addition, a Gaussian pattern of spot energy is suggested when fragmenting hard cataracts.

Automated and subjective refraction with monofocal, multifocal, and EDOF intraocular lenses: review.

Automated refraction (Scheiner principle) is universally used to start a visual examination. Although the results are reliable in eyes implanted with monofocal intraocular lenses (IOLs), they may be less precise with multifocal (mIOL) or extended depth-of-focus (EDOF) IOLs and can even indicate a refractive error that does not clinically exist. Autorefractor results with monofocal, multifocal, and EDOF IOLs were investigated through literature search analyzing the papers reporting the difference between automated and clinical refraction. The average difference ranged between -0.50 diopter (D) and -1.00 D with most mIOL and EDOF IOLs. The differences in astigmatism were generally much lower. Autorefractors using infrared light cannot measure eyes with high technology IOLs precisely because of the influence of the refractive or of the diffractive near add. The systematic error induced with some IOLs should be mentioned in the IOL label to prevent possible inappropriate refractive procedures to treat apparent myopia.

Acuity and Quality of Vision in Eyes with Epithelial Basement Membrane Dystrophy after Regular Pseudophakia.

PURPOSE: This retrospective case-control study was conducted to quantitatively and qualitatively assess the visual impairment in eyes with Epithelial Basement Membrane Dystrophy (EBMD) after regular cataract surgery. METHODS: EBMD pseudophakic eyes were compared with matched pseudophakic eyes free from surface disorders. At least 3 weeks after surgery we evaluated uncorrected and best-corrected distance visual acuity (UDVA and CDVA), objective aberrometry, Point Spread Function (PSF), Modulation Transfer Function (MTF), and patient complaints. RESULTS: Twenty-five EBMD eyes and 25 control eyes (13 patients per group) were included. Nine patients per group had a monofocal IOL, and four patients had a trifocal IOL. All the EBMD patients complained of postoperative blurred vision with ocular discomfort; intensive use of lubricants induced subjective improvement only in eyes with monofocal IOLs. Postoperative mean UDVA was 0.19 ± 0.16 LogMAR in the EBMD eyes and 0.11 ± 0.04 LogMAR in the control group (p = 0.016). Mean CDVA was 0.18 ± 0.15 LogMAR in the EBMD eyes and 0.06 ± 0.04 LogMAR in the control eyes (p = 0.001). The PSF curve width was significantly worse in the EBMD group (p < 0.001). The MTF cut-off value was lower in the EBMD group than in the control group (p < 0.001). CONCLUSION: After cataract removal, eyes with EBMD had significantly lower UDVA and CDVA than controls. All the aberrometric parameters were significantly worse in EBMD cases. EBMD patients complained about their postoperative visual outcome, while control patients did not.

Refractive Outcome and 5-Year Capsulotomy Rate of Hydrophobic and Hydrophilic IOLs with Similar Optical Design: A Contralateral Study.

INTRODUCTION: To compare the short-term visual and aberrometric outcomes and the long-term capsulotomy incidence in a cohort of patients receiving IOLs with similar structural profile but with a hydrophobic matrix in one eye (PHOB group) and a hydrophilic matrix in the other one (PHIL group). METHODS: In this retrospective, contralateral study, 26 patients sequentially undergoing phacoemulsification were implanted as mentioned above. Refraction and aberrometry were evaluated 6 months after surgery. For the quality of vision, the Hartmann-Shack optical aberration, Double-Pass Modulation Transfer Function (MTF), contrast sensitivity, and dysphotopsia results were compared. Capsulotomy was ascertained and dated by medical chart revision or phone call. RESULTS: All the considered quantitative and qualitative visual parameters tested statistically comparable between PHIL and PHOB group. After 5 years, four patients (16.7%) in the PHOB group and five patients (20.8%) in the PHIL group underwent a Nd:YAG posterior capsulotomy (P > 0.5). CONCLUSION: In this contralateral comparative study, the hydrophobic and hydrophilic matrix of the IOL similarly influenced the visual and aberrometric outcomes. Also the long-term laser capsulotomy incidence did not statistically differ between groups. The posterior IOL profile, rather than matrix hydrophilia, could consistently influence the posterior capsule opacification.

One-dioptre toric IOL versus spherical IOL in eyes with low preoperative corneal astigmatism.

PURPOSE: To investigate the advantages/disadvantages of a 1.0 D toric IOL vs spherical IOL after regular phacoemulsification in eyes with preoperative astigmatism ≤ 1 D. METHODS: Retrospective comparative series involving pseudophakic eyes with preoperative topographic astigmatism ≤ 1.0 D implanted either with monofocal 1.0 D Toric IOL (T-group), or with spherical IOL (S-group). The postoperative refractive astigmatism (PRA, i.e. surgically induced + corneal) was the main outcome; also considered in the analyses were the uncorrected and best-corrected distance visual acuity (VA). The data were referred to the last postoperative follow-up visit, 2 to 4 months after surgery. RESULTS: A total of 60 eyes were included: 30 in the T-group and 30 in the S-group, matched for patient's age, laterality, and axial length. Before surgery, the mean corneal astigmatism was 0.62 ± 0.39 D in the T-group and 0.54 ± 0.33 D in the S-group (p = 0.4). In the S-group, PRA was 0.73 ± 0.37 D, higher than the corresponding preoperative corneal astigmatism (p = 0.040). In the T-group, PRA was 0.58 ± 0.31 D; the variation was not statistically significant. Uncorrected VA was significantly better in the T-group vs the S-group (p = 0.007), and the best-corrected VA was comparable in the two groups. CONCLUSION: The present study indicated that in eyes with very low preoperative astigmatism, 1.0 D toric IOLs were able to limit the increase of the PRA instead of those observed with the spherical IOLs. This could support the better uncorrected VA recorded in the T-group.

Clinical and aberrometric evaluation of a new extended depth-of-focus intraocular lens based on spherical aberration.

PURPOSE: To compare the refractive, visual, and aberrometric results with a new extended depth-of-focus intraocular lens (EDOF IOL) based on alternating positive and negative spherical aberration in the central 3.0 mm optical zone and an aspheric monofocal IOL of the same platform. SETTING: Ophthalmology, University Hospital of Verona, Italy. DESIGN: Prospective case series. METHODS: Cataract patients free from other ocular disease had bilateral implantation of the EDOF Mini Well IOL or the monofocal Mini IOL. Four to 6 weeks after second-eye surgery, the refraction, visual acuity, defocus curve, contrast sensitivity, and photic symptoms were assessed. Wavefront analysis was performed. The primary endpoint of was the amplitude of the dioptric interval for 0.1 logarithm of the minimum angle of resolution (logMAR) visual acuity. The secondary endpoint was an aberration comparison between the two IOLs. RESULTS: The study comprised two groups of 25 patients each. The corrected distance visual acuity was better with the monofocal IOL by 0.02 logMAR (P = .03). The 0.1 logMAR dioptric interval was 2.0 diopters (D) for the EDOF IOL and 1.0 D for the monofocal IOL (P < .001). The mean CDVA at -2.0 defocus was 0.15 logMAR ± 0.08 (SD) and 0.52 ± 0.14 logMAR, respectively (P < .001). There was no difference in contrast sensitivity or photic symptoms. The optical aberrations at 4.0 mm and 6.0 mm aperture diameters were similar in the two groups. CONCLUSION: The EDOF IOL based on spherical aberration provided greater depth of focus than the aspheric monofocal IOL without increasing optical aberrations and with few photic symptoms.

Functional assessment of a new extended depth-of-focus intraocular lens.

BACKGROUND/OBJECTIVE: This study aimed to investigate the visual performance of a new extended depth-of-focus intraocular lens (EDOF-IOL). SUBJECTS/METHODS: In this multicenter, prospective, observational study, we enrolled 97 patients who underwent cataract surgery or refractive lens exchange with implantation of the Mini Well EDOF-IOL (SIFI, Italy). Patients underwent postoperatively the following examinations between 4 and 8 weeks after surgery: corrected distance visual acuity (CDVA), reading speed with Radner's chart, distance-corrected near visual acuity (DCNVA), defocus curve, contrast sensitivity, and haloes quantitative assessment. RESULTS: In the whole sample, the mean monocular CDVA and DCNVA were, respectively, 0.02 ± 0.07 logMAR and 0.38 ± 0.15 logRAD (logarithm of the reading acuity determination). In the 67 bilaterally implanted patients, binocular CDVA and DCNVA were better (0.00 ± 0.05 logMAR and 0.26 ± 0.13 logRAD) than the corresponding monocular values (p = 0.02 and p = 0.0002, respectively). Ninety-two percent of patients bilaterally implanted reached a binocular reading speed >80 words per minute at a 0.5 logRAD print size (corresponding to the common book print size). The defocus curves showed that the EDOF-IOL provided increased depth of focus through 2.0 D of defocus, with the best performance at 1.0 and 1.5 D. Contrast sensitivity was within normal limits at all spatial frequencies. The mean visual disturbance index was 0.08 ± 0.12, suggesting low night visual disturbances. CONCLUSIONS: The new EDOF-IOL provided good visual acuity for distance, intermediate, and near vision, with no loss of contrast sensitivity and low risk of night visual disturbances.

A New Extended Depth of Focus Intraocular Lens Based on Spherical Aberration.

PURPOSE: To describe a new extended depth of focus intraocular lens (IOL) design offering multifocality by the variation of spherical aberration in the central optical zone. METHODS: The new IOL (Mini WELL; SIFI, Catania, Italy) is an aspheric IOL with positive spherical aberration in the central 2-mm zone and negative spherical aberration in the pericentral 1-mm annulus, the amount of which was determined by specific optic calculation. The new IOL design was tested at the optical bench to investigate depth of focus and sensitivity to tilt, decentration, and angle Kappa. Visual acuity simulations were obtained from distance (4 m) to near (0.5 m). RESULTS: Modulation transfer function (MTF) for a 3-mm pupil was 0.35 to 0.40 for distance vision and 0.25 to 0.30 for intermediate and near vision. MTF for a 4.5-mm pupil was 0.40 to 0.55 and 0.10 to 0.20, respectively. These values were not influenced by tilt up to ±2.5°, by decentration up to ±0.5 mm, or by angle Kappa up to 9°. Visual acuity simulations indicated good visual acuity up to 2.00 D of pseudoaccommodation. CONCLUSIONS: The new IOL with double spherical aberration in the central 3-mm zone offered good MTF over a wide dioptric interval, suggesting good visual acuity between 4 m and 50 cm. This extended depth of focus IOL with no diffractive rings is expected to produce lower unwanted optical phenomena than current multifocal IOLs. [J Refract Surg. 2017;33(6):389-394.].

Enhancement of tumor cell susceptibility to natural killer cell activity through inhibition of the PI3K signaling pathway.

Natural killer (NK) cells are the primary effectors of the innate immune response against virus-infected cells or cells that have undergone malignant transformation. NK cells recognize their targets through a complex array of activating and inhibitory receptors, which regulate the intensity of the effector response against individual target cells. However, many studies have shown that tumor cells can escape immune cell recognition through a variety of mechanisms, developing resistance to NK cell killing. Using a lentiviral shRNA library, we previously demonstrated that several common signaling pathways modulate susceptibility of tumor cells to NK cell activity. In this study, we focused on one of the genes (PI3KCB), identified in this genetic screen. The PI3KCB gene encodes an isoform of the catalytic subunit of PI3K called P110ß. The PI3K pathway has been linked to diverse cellular functions, but has never been associated with susceptibility to NK cell activity. Gene silencing of PI3KCB resulted in increased susceptibility of several tumor cell lines to NK cell lytic activity and induced increased IFN-γ secretion by NK cells. Treatment of primary tumor cells with two different PI3K inhibitors also increased target cell susceptibility to NK cell activity. These effects are due, at least in part, to modulation of several activating and inhibitory ligands and appear to be correlated with PI3K signaling pathway inhibition. These findings identify a new and important role of PI3KCB in modulating tumor cell susceptibility to NK cells and open the way to future combined target immunotherapies.

Investigating the ocular temperature rise during femtosecond laser lens fragmentation: an in vitro study.

PURPOSE: To investigate the trend of temperature variation during lens fragmentation simulated by a femtosecond laser on an in vitro eye model. METHODS: In our experimental study, a convex cylinder of gelatinous material, usually employed in femtosecond laser calibration, was used to simulate both an anterior segment and a crystalline lens during fragmentation performed with the Victus femtosecond laser (Technolas Perfect Vision GmbH, Germany; Bausch + Lomb Incorporated, USA). Two radiated energies (7000 nJ and 9000 nJ) and three cutting patterns (crosses, circles and cross + circle) were applied. Trends of temperature variation as a function of time were obtained using a T-type thermocouple. RESULTS: The maximum value of temperature rise during lens fragmentation ranged from 3.53 to 5.13 °C; the rise was directly proportional to the intensity of the radiated energy (7000 nJ or 9000 nJ) and the cutting pattern performed. This behavior was experimentally represented by an asymmetric function with a characteristic bell curve shape, whereas it was mathematically described by a transport diffusive model. CONCLUSIONS: Since the temperature rise at the fragmentation volume base resulted to be around 5 °C in our in vitro study, lens fragmentation performed using the Victus femtosecond laser might be considered safe form a thermal point of view.

Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression.

Inhibition of JAK1 or JAK2 in human tumor cells was previously shown to increase susceptibility of these cells to NK cell lysis. In the present study, we examined the cellular mechanisms that mediate this effect in hematopoietic tumor cell lines and primary tumor cells. Incubation of tumor cells with supernatant from activated NK cells or interferon-gamma (IFNγ)-induced activation of pSTAT1 and increased expression of PD-L1 without altering expression of other activating or inhibitory NK cell ligands. These functional effects were blocked by chemical JAK inhibition or shRNAs targeting JAK1, JAK2 or STAT1. Inhibition of IFNγ signaling also prevented the upregulation of PD-L1 and blocking PD-L1 resulted in increased tumor lysis by NK cells. These results show that NK cell activation and secretion of IFNγ results in activation of JAK1, JAK2 and STAT1 in tumor cells, resulting in rapid up-regulation of PD-L1 expression. Increased expression of PD-L1 results in increased resistance to NK cell lysis. Blockade of JAK pathway activation prevents increased PD-L1 expression resulting in increased susceptibility of tumor cells to NK cell activity. These observations suggest that JAK pathway inhibitors as well as PD-1 and PD-L1 antibodies may work synergistically with other immune therapies by preventing IFN-induced inhibition of NK cell-mediated tumor cell lysis.

Visual acuity and refraction with a diffractive multifocal toric intraocular lens.

PURPOSE: To evaluate clinical outcomes and optical performance of the AT Lisa 909M diffractive multifocal toric intraocular lens (IOL). SETTING: Multicenter study. DESIGN: Cohort study. METHODS: The measured outcomes included refractive error; distance, near (40 cm), and intermediate (60 cm and 80 cm) visual acuities; defocus curve; rotational stability; and monocular and binocular photopic and mesopic contrast sensitivity. Astigmatism was evaluated by Alpins vector analysis. RESULTS: The multifocal toric IOL was implanted in 284 eyes of 142 patients. At 6 months, 89.4% of eyes were within ±1.00 diopter (D) of emmetropia. The mean refractive cylinder decreased from -2.39 D ± 1.48 (SD) to -0.49 ± 0.53 D; it was lower than 1.00 D in 80.9% of eyes. The mean visual acuities (logMAR) were monocular uncorrected distance 0.16 ± 0.22, monocular corrected distance 0.04 ± 0.15, binocular corrected distance -0.00 ± 0.09; monocular uncorrected near 0.21 ± 0.22, monocular corrected near 0.08 ± 0.16, binocular distance-corrected near 0.07 ± 0.14; intermediate at 60 cm (80 cm): monocular uncorrected 0.16 ± 0.21 (0.09 ± 0.21), monocular distance corrected 0.13 ± 0.19 (0.07 ± 0.20), and binocular distance corrected 0.07 ± 0.17 (0.00 ± 0.18). At 3 months and 6 months, 95.8% of IOLs showed no rotation over 5 degrees. CONCLUSIONS: This is the largest study yet on the first commercially available diffractive multifocal toric IOL. Results confirm its efficacy, predictability, and safety in restoring distance, near, and intermediate vision and allowing patients with significant levels of corneal astigmatism to achieve spectacle independence. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.