Dupilumab-Associated Adverse Events During Treatment of Allergic Diseases.

Among the new biological therapies for atopic diseases, dupilumab is a fully human monoclonal antibody directed against IL-4Rα, the common chain of interleukin-4 and interleukin-13 receptors. Dupilumab showed clinical improvements in patients with atopic dermatitis, asthma, and chronic rhinosinusitis and is currently under development for other indications. While dupilumab is considered to be well tolerated, a number of recent publications have reported various adverse events. This review aims to summarize the current knowledge about these adverse events, which may help clinicians to improve the follow-up of patients on dupilumab. Injection-site reactions are the most common reported adverse event. However, dupilumab has also been shown to cause ophthalmic complications (e.g., dry eyes, conjunctivitis, blepharitis, keratitis, and ocular pruritus), head and neck dermatitis, onset of psoriatic lesions, progression of cutaneous T-cell lymphoma exacerbation, alopecia areata, hypereosinophilia, and arthritis. Most are managed during dupilumab treatment continuation, but some (e.g., severe conjunctivitis) may result in a discontinuation of treatment. Their molecular origin is unclear and requires further investigations. Among other hypothesis, it has been suggested that T helper (Th)2-mediated pathway inhibition may worsen Th1/Th17-dependent immune responses. An ophthalmological examination for the presence of potential predictive indicators of ophthalmic adverse events is recommended before initiation of dupilumab therapy.

Transepithelial Corneal Cross-linking With Supplemental Oxygen in Keratoconus: 1-Year Clinical Results.

PURPOSE: To evaluate the efficacy and safety of transepithelial corneal cross-linking (CXL) with supplemental oxygen. METHODS: This was a prospective, non-comparative, pilot cohort study conducted at the National Reference Center for Keratoconus (Toulouse, France) on patients with progressive keratoconus. Transepithelial, pulsed, accelerated CXL was performed in an oxygen-rich atmosphere. Oxygen goggles were applied to the eyes to maintain a high level of oxygen during treatment. The main efficacy outcome was the mean change from baseline in maximum keratometry (Kmax) and the secondary outcomes were the mean changes in flat keratometry (K1), steep keratometry (K2), mean keratometry (Km), corrected distance visual acuity (CDVA), uncorrected distance visual acuity (UDVA), and demarcation line depth. The safety outcomes were the incidence of adverse events, the mean change in pachymetry, and endothelial cell count. RESULTS: Thirty-four eyes of 34 patients were included. At 12 months postoperatively, the Kmax decreased by 1.56 ± 1.71 diopters (D) (P < .0001) and CDVA improved by 0.093 ± 0.193 logMAR (P < .02). The K2 and Km decreased by 0.51 ± 1.03 D (P < .02) and 0.40 ± 0.78 D (P < .01), respectively. There was no change in K1 and UDVA. The most frequent adverse event was corneal haze (64.78%). There were neither cases of infectious keratitis or loss of more than two lines in CDVA nor changes in pachymetry or endothelial cell count. CONCLUSIONS: Transepithelial CXL performed in an oxygen-rich atmosphere results in improved Kmax and CDVA with good safety. These promising findings suggest that this procedure could be safe and capable of halting the progression of keratoconus. [J Refract Surg. 2021;37(1):42-48.].

Transepithelial photorefractive intrastromal corneal crosslinking versus photorefractive keratectomy in low myopia.

PURPOSE: To compare the outcomes of transepithelial photorefractive intrastromal corneal crosslinking (CXL) and photorefractive keratectomy (PRK) in eyes with low myopia. SETTING: Purpan Hospital, Toulouse, France. DESIGN: Prospective case series. METHODS: Myopic patients with a manifest refraction spherical equivalent (MRSE) of -1.00 to -2.50 diopters (D) and a cylindrical component of plano to -0.75 D were included. The dominant eye had PRK (PRK eyes). The nondominant eye had transepithelial photorefractive intrastromal CXL with riboflavin (ParaCel Part 1 and 2), 30 mW/cm2 pulsed ultraviolet-A irradiation centered on the pupil (Mosaic System) for 16 minutes and 40 seconds, and a supplemental oxygen delivery mask (CXL eyes). The primary outcome measure was the change in the MRSE. Other outcome measures were the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean keratometry, and endothelial cell count (ECC) over a 6-month follow-up. Adverse events were assessed. RESULTS: Nineteen patients were included. By 6 months, the mean MRSE had decreased by 0.72 D ± 0.42 (SD) in CXL eyes and by 1.35 ± 0.46 D in PRK eyes (P < .001). The mean change in UDVA was -0.35 ± 0.21 logarithm of the minimum angle of resolution (logMAR) in CXL eyes and -0.66 ± 0.19 logMAR in PRK eyes (P < .001). No complications were reported. The change in the ECC and CDVA was not statistically significant. CONCLUSIONS: Photorefractive keratectomy provided better visual and refractive outcomes than transepithelial photorefractive intrastromal CXL. Transepithelial photorefractive intrastromal CXL, however, showed the potential refractive effect of CXL but with a limited magnitude of myopic correction.

Primary sulcus implantation of a diffractive multifocal pseudophakic piggyback intraocular lens.

PURPOSE: To evaluate the efficacy and safety of the combined implantation of a monofocal intraocular lens (IOL) in the capsular bag with a diffractive multifocal IOL designed for sulcus placement (Reverso). SETTING: Purpan Hospital, Toulouse, and Helios Clinic, Saint-Jean-de-Luz, France. DESIGN: Prospective case series. METHODS: The multifocal IOL piggyback IOL was implanted in the sulcus during cataract surgery. Visual acuity, defocus curve, contrast sensitivity, IOL positioning, and patient satisfaction were assessed with 1-year follow-ups. RESULTS: Fifty-four eyes of 27 patients were included. At 1-month, monocular uncorrected distance (UDVA) and near (UNVA) visual acuities were 0.13 logarithm of the minimum angle of resolution (logMAR) ± 0.18 (SD) and 0.20 ± 0.16 logMAR, respectively. Binocular UDVA and UNVA were 0.03 ± 0.06 and 0.12 ± 0.08 logMAR, respectively. At 1 year, the mean monocular logMAR UDVA, corrected distance visual acuity, UNVA, and corrected near visual acuity were 0.10 ± 0.11, 0.02 ± 0.06, 0.18 ± 0.12, and 0.13 ± 0.08, respectively. The defocus curve and contrast sensitivity values were comparable to those obtained with other multifocal IOLs. On Scheimpflug imaging, the mean distance between the sulcus multifocal IOL and the monofocal IOL was 517 ± 141 µm. At 1 year, ultrasound biomicroscopy showed an annular fibrosis of the anterior capsule in 94.4% of the eyes. Complications included 1 posttraumatic IOL decentration and 1 slight corectopia. Eighty-nine percent of patients reported satisfaction. CONCLUSIONS: The piggyback implantation of this multifocal IOL seemed to be safe and effective. It might provide similar results as a primary in-the-bag multifocal IOL, with the advantage of reversibility that might extend primary or secondary implantation.

Customized Topography-Guided Corneal Collagen Cross-linking for Keratoconus.

PURPOSE: To compare the efficacy and safety of topography-guided corneal collagen cross-linking (TG-CXL) to conventional corneal CXL (C-CXL) in progressive keratoconus. METHODS: In this prospective, nonrandomized clinical trial, 60 eyes of 60 patients were scheduled to receive either TG-CXL (30 eyes with deepithelialization focused on the cone, riboflavin application for 10 minutes, and 30 mW/cm2 pulsed ultraviolet-A irradiance pattern according to topography) or C-CXL (30 eyes treated in accordance with the Dresden protocol). Patients were observed for 1 year postoperatively. Maximum keratometry (Kmax), mean keratometry in the inferior part of the cornea (I index), corrected distance visual acuity (CDVA), demarcation line observed in optical coherence tomography, and nerves and cell densities analyzed by confocal microscopy were compared preoperatively and at 1 year postoperatively. RESULTS: The difference was significant for both Kmax (P < .01) and I index (P < .01) between the two groups. CDVA improved significantly in the TG-CXL (0.2162 ± 0.2495 logMAR, P < .05) versus the C-CXL (0.2648 ± 0.2574 logMAR, P = .104) group. A stromal demarcation line was observed in both treatment groups, with similar depth at the top of the cone (P = .391), but it was shallower at the surrounding area in the TG-CXL group (P < .0001). Stromal evaluation by confocal microscopy showed less damage and faster healing in the surrounding area than on the cone area in the TG-CXL group. CONCLUSIONS: At 1 year postoperatively, TG-CXL seems to be as safe as C-CXL with stronger flattening in Kmax and I index and better improvement in CDVA. TG-CXL induces a biological gradient between the cone and the surrounding area that facilitates nerve and cell recovery. [J Refract Surg. 2017;33(5):290-297.].

Relationship between induced spherical aberration and depth of focus after hyperopic LASIK in presbyopic patients.

OBJECTIVE: To evaluate to what extent the modification of corneal asphericity to induce spherical aberration (SA) can improve the depth of focus and to determine whether preoperative adaptive optics assessment (Voptica SL) can predict an optimal SA value for each patient. DESIGN: Comparative, prospective clinical trial with paired eye control. PARTICIPANTS: Patients ≥45 years old who are hyperopic from +1.00 to +2.50 diopters (D), with eyes suitable for LASIK surgery. INTERVENTION: Bilateral hyperopic LASIK surgery using a 200-Hz Allegretto excimer laser. The dominant eye was operated using a conventional profile. The nondominant eye was programmed with an aspheric ablation profile and -0.75 D monovision. MAIN OUTCOME MEASURES: Primary outcome was the correlation between postoperative SA and depth of focus, defined as the pseudo-accommodation value (PAV = [1/reading distance {m}] - minimum addition [D]). Main secondary outcome was the comparison of depth of focus between patients with an induced SA close to the optimal one (group 1), patients with an induced SA far from the optimal one (group 2), and patients for whom SA induction did not increase the depth of focus (control group). RESULTS: We included 76 patients. Between preoperative and postoperative assessment, the mean increase of distance-corrected PAV for near vision was +0.25±0.64 D (P < 0.001) for dominant eyes and +0.63±0.55 D (P < 0.001) for nondominant eyes. As the level of negative or positive postoperative SA increased, PAV for intermediate and near vision increased. Among the 37 eyes that followed the preoperative adaptive optics assessment, the mean PAV increase at near was significantly higher (P < 0.05) in group 1 (0.93±0.50 D) than in group 2 (0.46±0.42 D) and than in the control group (0.35±0.32 D). The mean optimal SA value determined by the dynamic simulation procedure to optimize the depth of focus was -0.18±0.13 µm at 4.5 mm. CONCLUSIONS: Aspheric hyperopic LASIK can increase the depth of focus without impairing far vision, but this benefit would be maximal and reproducible if we could define and achieve an optimal SA value determined by preoperative assessment using an adaptive optics instrument.