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.

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.

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.

Comparison of Objective and Subjective Visual Outcomes Between Pentafocal and Trifocal Diffractive Intraocular Lenses.

PURPOSE: To compare the clinical and aberrometric outcomes obtained with a new diffractive pentafocal intraocular lens (IOL) and a diffractive trifocal IOL. METHODS: Patients bilaterally implanted with the pentafocal Intensity SeeLens IOL (Hanita Lenses) (n = 30) and the trifocal FineVision POD F IOL (PhysIOL) (n = 30) during cataract surgery were studied after 1 month for refraction, visual acuity, defocus curve, contrast sensitivity, Hartmann-Shack aberration, and double-pass aberration. The Quality of Vision (QoV) questionnaire was used to evaluate visual comfort. RESULTS: Distance and near visual acuities were similar with the two IOLs, but distance-corrected intermediate visual acuity was better with the Intensity IOLs (0.03 ± 0.04 vs 0.11 ± 0.04 logMAR in the FineVision eyes, P < .01). The difference between objective and subjective refraction was more myopic for the Intensity IOL (-1.15 vs -0.29 diopters [D]). The defocus curve was flatter with the Intensity IOL. Contrast sensitivity was similar in both IOLs. Hartmann-Shack aberration and double-pass aberration were similar, but the modulation transfer function cut-off value was worse with the Intensity IOL: 11.6 ± 2.7 vs 15.3 ± 4.9 (P < .01). QoV scores were better with the Intensity IOL, in particular for glare, halos, and starburst. CONCLUSIONS: In this comparative series, the pentafocal Intensity IOL provided better intermediate vision and better defocus curve than the FineVision IOL, with comparable distance and near vision. The optical disturbances as reported by the patients were higher with the FineVision IOL. Additional studies will better define the aberration profile obtained with the pentafocal IOL. [J Refract Surg. 2024;40(9):e604-e613.].

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.

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.

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.

Combined CD4+ donor lymphocyte infusion and low-dose recombinant IL-2 expand FOXP3+ regulatory T cells following allogeneic hematopoietic stem cell transplantation.

CD4(+)CD25(+)FOXP3(+) regulatory T cells (Treg) successfully control graft-versus-host-disease (GVHD) in animal models. In humans, incomplete reconstitution of Treg after allogeneic hematopoietic stem cell transplantation (HSCT) has been associated with chronic GVHD (cGVHD). Recent studies have demonstrated that interleukin (IL)-2 infusions expand Treg in vivo. However, the effectiveness of this therapy depends on the number of cells capable of responding to IL-2. We examined the effect of low-dose IL-2 infusions on Treg populations after HSCT in patients who also received infusions of donor CD4(+) lymphocytes. Utilizing FOXP3 as a Treg marker, we found that patients who received CD4+DLI concomitantly with IL-2 had greater expansion of Treg compared to patients who received IL-2 (P = .03) or CD4(+)DLI alone (P = .001). FOXP3 expression correlated with absolute CD4(+)CD25(+) cell counts. Moreover, expanded CD4(+)CD25(+) T cells displayed normal suppressive function and treatment with CD4(+)DLI and IL-2 was not associated with GVHD. This study suggests that administration of low-dose IL-2 combined with adoptive CD4(+) cellular therapy may provide a mechanism to expand Treg in vivo.

AcrySof phakic angle-supported intraocular lens for the correction of moderate-to-high myopia: one-year results of a multicenter European study.

PURPOSE: To investigate the safety and effectiveness of the AcrySof phakic angle-supported intraocular lens (IOL) (Alcon Laboratories, Inc., Fort Worth, TX) for correction of moderate-to-high myopia in adults. DESIGN: One-year interim analysis of a phase 3, nonrandomized, open-label, prospective, multicenter European clinical study. PARTICIPANTS: A total of 190 subjects (190 eyes) with moderate-to-high myopia. The preoperative mean manifest refraction spherical equivalent (MRSE) was -10.38 diopters (D) +/-2.43 standard deviation (SD). METHODS: Unilateral implantation of the AcrySof phakic angle-supported IOL. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity (BSCVA), uncorrected distance visual acuity (UCVA), predictability and stability of MRSE, adverse events, and endothelial cell density. RESULTS: Of 190 subjects enrolled, 161 completed the 1-year postoperative visit. No subjects lost > or =2 lines BSCVA. A UCVA of 20/20 or better was achieved by 57.8%; 99.4% had 20/40 or better. A BSCVA of 20/32 or better was achieved by 100% of subjects; 85.7% had 20/20 or better. The mean MRSE was -0.23 D (+/-0.50 D: -2.50 to 0.75 D). Residual refractive error was within +/-1.0 D from the target for 95.7% of subjects and within +/-0.5 D for 72.7% of subjects. The overall mean percentage change in central endothelial cell density 1 year after surgery was -4.77+/-8.04% (n = 139). No pupil ovalization, pupillary block, or retinal detachment events were observed. CONCLUSIONS: The AcrySof phakic angle-supported IOL yielded excellent refractive correction and predictability with acceptable safety in subjects with moderate-to-high myopia. These 1-year interim analysis findings demonstrate preliminary support for the safety and efficacy of this IOL.

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.

Side-port stabilizer to assist implantation of microincision intraocular lenses.

We describe a new instrument for incision-assisted implantation of microincision intraocular lenses (IOLs). The instrument is a short nail, smooth and oval, that is inserted into the side-port incision to stabilize the eye during IOL implantation. The head prevents deep penetration and escape of the ophthalmic viscosurgical device through the incision. The instrument was safe and effective in its initial use; the 1 failure was due to the close proximity of the side port and the main incision.

Spherical aberration and coma with an aspherical and a spherical intraocular lens in normal age-matched eyes.

PURPOSE: To study optical aberrations in eyes having uneventful cataract surgery and in-the-bag implantation of an aspherical Tecnis Z9000 intraocular lens (IOL) (AMO) or a spherical CeeOn Edge 911 IOL (Pharmacia) and compare the results with those in a group of phakic age-matched eyes. SETTING: Ophthalmic Unit, Hospital and University of Verona, Verona, Italy. MATERIALS: Three groups, each with 30 patients (30 eyes), were examined with the Topcon KR-9000PW topographer/aberrometer. Spherical aberration and coma were analyzed in detail for 4.0 mm optical zone. Internal values were obtained by subtracting corneal aberrations from ocular aberrations. Point spread function and modulation transfer function (MTF) were considered for optical quality. RESULTS: The mean internal spherical aberration Z(4)(0) was -0.048 microm +/- 0.017 (SD) in the Tecnis group, +0.033 +/- 0.026 microm in the 911 Edge group (P<.001), and -0.013 +/- 0.056 microm in the phakic group (P = .149). The mean internal vertical coma Z(3)(-1) was 0.087 +/- 0.056 microm, 0.054 +/- 0.043 microm (P = .005), and 0.044 +/- 0.044 microm (P<.001), respectively. The internal horizontal coma Z(3)(+1) showed a similar pattern; however, total resulting coma was similar in the 3 groups. The mean Strehl ratio was 0.284 +/- 0.166 in the Tecnis group, 0.145 +/- 0.077 in the 911 Edge group (P<.01), and 0.164 +/- 0.097 in the phakic group (P<.01). The MTF curve was better in the Tecnis group (P<.001). CONCLUSIONS: After uneventful implantation, the aspherical IOL yielded better ocular aberration and optical quality results than the spherical IOL. Induced coma was somewhat higher in the Tecnis group; however, the overall results were not affected. Physiologic IOL decentration after correct in-the-bag implantation did not negate the advantages of asphericity.

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.].

Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion.

Donor lymphocyte infusions (DLI) provide effective therapy for patients with multiple myeloma who have relapsed after allogeneic bone marrow transplantation. However, the immunological mechanisms of the graft-versus-myeloma (GVM) effect have not been defined, and the target antigens of this response have not been identified. Molecular analysis of CDR3 Vbeta repertoire after CD4+ DLI demonstrated previously that the development of GVM and graft-versus-host-disease (GVHD) were associated with the clonal expansion of distinct T-cell populations in patient peripheral blood. In the current study, we undertook a molecular and functional characterization of GVM- and GVHD-associated T-cell clones. T-cell clones associated with GVM were detectable by clone-specific PCR at a low level in peripheral blood before DLI and expanded approximately 10-fold after DLI. In contrast, T-cell clones associated with GVHD were not detectable before DLI or before the development of clinical GVHD. Two T-cell clones associated with GVM were isolated and expanded in vitro, allowing their phenotypic and functional characterization. Both GVM clones were derived from donor cells and had a CD3+CD8+CD4- phenotype. One GVM clone specifically recognized patient myeloma cells in an HLA class I-restricted manner, but was not reactive with patient normal bone marrow cells or patient EBV transformed B cells. Taken together, these findings suggest that the GVM response is mediated by donor-derived CD8+ T-cell clones with antimyeloma specificity that may be present before DLI. In contrast, T-cell clones associated with GVHD are expanded de novo after DLI.