Multicenter prospective observational study of dupilumab-induced ocular events in atopic dermatitis patients.

BACKGROUND: Although ocular adverse events are frequent in AD patients treated with dupilumab, their characterization remains limited due to a lack of prospective studies with a systematic ophthalmological examination. OBJECTIVE: To examine the incidence, characteristics and risk factors of dupilumab-induced ocular adverse events. METHODS: A prospective, multicenter, and real-life study in adult AD patients treated with dupilumab. RESULTS: At baseline, 27 out of 181 patients (14.9%) had conjunctivitis. At week 16 (W16), 25 out of 27 had improved their conjunctivitis and 2 remained stable and 34 out of 181 patients (18.7%) had dupilumab-induced blepharoconjunctivitis: either de novo (n = 32) or worsening of underlying blepharoconjunctivitis (n = 2). Most events (27/34; 79.4%) were moderate. A multivariate analysis showed that head and neck AD (OR = 7.254; 95%CI [1.938-30.07]; p = 0.004), erythroderma (OR = 5.635; 95%CI [1.635-21.50]; p = 0.007) and the presence of dry eye syndrome at baseline (OR = 3.51; 95%CI [3.158-13.90]; p = 0.031) were independent factors associated with dupilumab-induced blepharoconjunctivitis. LIMITATIONS: Our follow-up period was 16 weeks and some late-onset time effects may still occur. CONCLUSION: This study showed that most dupilumab-induced blepharoconjunctivitis cases are de novo. AD severity and conjunctivitis at baseline were not found to be associated risk factors in this study.

COMPARING INTRAVITREAL AIR AND GAS FOR THE TREATMENT OF VITREOMACULAR TRACTION.

PURPOSE: To compare the effect of intravitreal injections of air with gas on vitreomacular traction (VMT) release and attempt to analyze predictive factors for success. METHODS: The medical records of patients with symptomatic VMT undergoing intravitreal injections (0.3 mL) of either octafluoropropane (C3F8) or air were retrospectively reviewed. The VMT release (primary end point) and the best-corrected visual acuity (secondary end point) were noted 1 month after injection. At baseline and 1 month after the injection, a macular optical coherence tomography was performed. RESULTS: Twenty-four eyes of 22 patients were included. Vitreomacular traction was released in 10 cases, 7 among 11 C3F8-injected eyes (63%) and 3 among 13 air-injected eyes (23%) (P = 0.045). In eyes with released VMT, ETDRS improved from 61 ± 35 (0-100) to 65 ± 37 (0-100) 1 month after the injection (P = 0.03). All patients with VMT release had a horizontal vitreomacular adhesion of less than 600 µm. Five eyes (23%) underwent vitrectomy after the injection of gas or air. CONCLUSION: Posterior vitreous detachment in VMT can be observed with both air and gas injection with a low complication rate. The occurrence of VMT release observed with air seemed to be less frequent than that observed with gas.

Dry eye disease after refractive surgery: comparative outcomes of small incision lenticule extraction versus LASIK.

PURPOSE: To compare small incision lenticule extraction (SMILE) versus LASIK for post-refractive dry eye disease. DESIGN: Prospective, comparative, nonrandomized clinical study. PARTICIPANTS: Thirty patients scheduled for bilateral myopic SMILE and 30 age-, sex-, and refraction-matched patients scheduled for bilateral myopic LASIK were enrolled and followed for 6 months after the surgery. METHODS: Complete evaluation of dry eye disease was performed at 1 and 6 months postoperatively, which included vision-related quality of life (Ocular Surface Disease Index [OSDI]), clinical examinations (tear film breakup time [TBUT], Schirmer I test, corneal staining), and tear osmolarity measurements, together with an overall severity score. Function and morphology of the corneal innervation were evaluated by corneal esthesiometry and subbasal nerve imaging using in vivo confocal microscopy (IVCM). MAIN OUTCOME MEASURES: Overall analysis of dry eye disease and corneal innervation. RESULTS: High incidence of mild to moderate dry eye disease was observed in both groups 1 month postoperatively, which remained significantly higher in the LASIK group than in the SMILE group 6 months after surgery (overall severity score [0-4]: 1.2±1.1 vs. 0.2±0.4, respectively, P < 0.01), leading to more frequent use of tear substitutes over the long term. Corneal sensitivity was better in SMILE than in LASIK eyes 1 month postoperatively (3.5±1.79 vs. 2.45±2.48, respectively, P < 0.01) and then recovered to statistically similar values at 6 months. Corneal nerve density, number of long fibers, and branchings as assessed by IVCM were significantly higher in the SMILE group compared with the LASIK group 1 and 6 months after surgery. Corneal sensitivity was negatively correlated with dry eye-related corneal damage (R² = 0.48, P < 0.01), and the long fiber nerve density was independently correlated with the OSDI score (R² = 0.50, P < 0.01) and the Schirmer test (R² = 0.21, P < 0.01) 6 months postoperatively. CONCLUSIONS: The SMILE procedure has a less pronounced impact on the ocular surface and corneal innervation compared with LASIK, further reducing the incidence of dry eye disease and subsequent degradation in quality of life after refractive surgery.

Revisiting the Use of Deep Temporalis Fascia Grafts in Ophthalmology.

PURPOSE: To report new indications for deep temporalis fascia (DTF) grafts in the ophthalmic field. METHODS: Monocentric retrospective interventional case series study. All the patients who underwent a DTF graft in an unpublished new indication over the study period (May 2020-October 2023) were included. For each patient, gender, age, graft indication, outcomes, complications, and follow-up duration were collected. In most cases, the DTF graft was covered by a vascularized flap. RESULTS: Eight patients underwent a DTF graft over the study period. The indications were: radiotherapy-induced scleral necrosis in three cases, tendinoplasty to replace the inferior rectus muscle tendon invaded by a locally advanced conjunctival carcinoma in one case, Ahmed glaucoma valve tube exposure in one case, intraocular lens with scleral fixation exposure in one case, orbital cerebrospinal fluid fistula (orbitorrhea) in one case, and post-traumatic complete corneal graft loss in one case. The DTF graft was successful in 87.5% of cases after a mean follow-up of 11.4 months. No complications were observed. CONCLUSIONS: DTF graft is a highly versatile graft that can be easily harvested. New indications for DTF grafts may include the repair of radiotherapy-induced scleral necrosis, the creation of oculomotor tendon and the temporary packing of large ocular tissue loss in an emergency context. Further studies with a longer follow-up are needed to confirm our preliminary results.

[Chemokines: new insights in the treatment of glaucoma and inflammatory diseases of the ocular surface]. / Les chimiokines : une nouvelle piste thérapeutique dans le glaucome et les maladies inflammatoires de la surface oculaire.

The celebrations of the 200th anniversary of Claude Bernard's birth (1813) give us the opportunity to recall all the pioneer work carried out by the great physiologist, which still remains relevant in both scientific and medical fields. The description that tissues are "floating in a liquid milieu" bringing survival molecules and allowing homeostasis, is particularly illustrated in the physiopathology of glaucoma. Second leading cause of blindness worldwide, glaucoma is an optic neuropathy mainly related to an increase of intraocular pressure. Degeneration of the trabecular meshwork, the filter that allows aqueous humor outflow from the eye, includes loss of trabecular cells, extracellular matrix remodeling, oxidative stress, and release of inflammatory cytokines, which are together the hallmarks of glaucoma. Although globally efficient, the topical treatments of glaucoma with eye drops containing active compounds produce, in the long-term, side effects mainly due to benzalkonium chloride, a preservative added to prevent bottle contamination. Such compound induces inflammatory processes. Thus, new data involving chemokines such as CXCL12, known to play a key role in inflammation and cellular crosstalk in the trabecular meshwork, offer new targets for the development of innovative treatments in glaucoma.

Roth spots in a Rendu-Osler-Weber syndrome.

PURPOSE: To describe the molecular diagnosis and atypical ocular presentation of a patient who suffered for a Rendu-Osler-Weber syndrome associated with juvenile polyposis (JP) syndrome. METHODS: This is a case report of a patient that underwent fundus examen, brain Magnetic Resonance Imaging (MRI) and arteriography. Genetic testing was performed by next-generation-sequencing (NGS). RESULTS: A 35-year-old woman presented with right hemiplegia with right homonymous lateral hemianopia and homolateral complete sensory deficit. She also had Roth spots in her left fundus. Genetic testing revealed a pathogenic variation in the heterozygous state in the SMAD-4 gene (c.1245_1248del). CONCLUSION: Hereditary Hemorrhagic Telangiectasia (HTT) also known as Rendu-Osler-Weber syndrome is a rare autosomal dominant disease which reveals mostly with epistaxis and cutaneous telangiectasias. Our clinical case reports Roth spots in the context of HTT associated with juvenile polyposis syndrome. SMAD-4 mutation may explain the presence of a carotid-ophthalmic aneurysm which is not a lesion usually found in HTT.

Identifying predictive factors for long-term visual recovery after corneal endothelial keratoplasty in Fuchs' dystrophy: Potential interaction between the corneal dysfunction and retinal status.

Introduction: Descemet membrane endothelial keratoplasty (DMEK) is the main treatment for Fuchs' dystrophy (FECD). The outcomes are excellent, but the final visual recovery may vary from patient to patient with sometimes no obvious reason of such a spread. Methods: We conducted a clinical prospective multicentric study to identify the predictive factors for the visual result 1 year after surgery. Eighty three patients (83 eyes) were included. Results: Postoperative BCVA after 1 year was 0.20 ± 0.18 logMAR. Logistic regression revealed that good visual recovery correlated negatively with preoperative central macular thickness (p < 0.001) and the need for rebubbling (p = 0.05), and positively with preoperative visual acuity (p = 0.009). Multivariate formula to predict the 1-year BCVA has been suggested. Discussion: Preoperative retinal status seems to be the main predictive factor for long-term visual result after DMEK. Our predictive multivariate model could assist in better informing the patient about the prognosis of the surgery, and in adjusting the therapeutic strategy also, further highlighting the essential collaboration between both cornea and retina subspecialists.

Tear film aberration dynamics and vision-related quality of life in patients with dry eye disease.

OBJECTIVE: Corneal and ocular wavefront aberrations were recorded together with clinical examination results and patient-reported vision-related quality-of-life evaluation results to define the relevance of dynamic optical analysis of the eye in dry eye disease (DED). DESIGN: Prospective and comparative clinical study. PARTICIPANTS: Forty DED patients and 40 age- and gender-matched control subjects. METHODS: Serial measurements of ocular and corneal higher-order aberrations (HOAs) after blink were performed for 10 seconds using the KR-1 aberrometer (Topcon, Clichy, France). Vision-related health-targeted quality of life was evaluated using the Ocular Surface Disease Index (OSDI) questionnaire. The clinical examination included tear film assessment (tear film break-up time and Schirmer I test), ocular surface damage assessment with the Oxford and van Bijsterveld indexes, and Meibomian dysfunction grading. Tear osmolarity also was measured. MAIN OUTCOME MEASURES: The time course of HOAs and modulation transfer function (MTF) was compared between groups and was analyzed in comparison with the OSDI and clinical data in DED patients. RESULTS: The root mean square of ocular and corneal total HOAs, particularly third-order aberrations, significantly increased over the 10-second period in DED patients, whereas no change occurred in controls. Analysis of MTF revealed progressive degradation of ocular optical quality resulting from loss of contrast at intermediate and high spatial frequencies in DED patients compared with controls. The progression index for corneal HOAs was correlated with the subjective index of patient-reported visual outcomes and with objective clinical findings of tear film and ocular surface damage. CONCLUSIONS: Objective measurement of the time course of HOAs may constitute a new single instrument to evaluate and manage patients with DED because it reliably reflects the completeness of the disease.

First use of a new rapid multiplex PCR system for the microbiological diagnosis and the clinical management of severe infectious keratitis: A case report.

Purpose: We report the use of a rapid multiplex polymerase chain reaction (PCR) system in the microbiological diagnosis and the therapeutic management of a severe bacterial keratitis case. Observations: During the management of a severe bacterial keratitis case, standard microbiological diagnostic methods were performed. At the same time, an additional ocular swab sampling from the cornea was performed and analyzed using two rapid multiplex PCR assays allowing the simultaneous detection of 29 different virus, yeast and bacteria genomes. Using combination of two rapid multiplex PCR systems, the microbiological diagnosis of a severe Pseudomonas aeruginosa induced keratitis was performed within 90 minutes after an ocular sampling. A rapid subsequent adaptation of local antibiotic treatment was performed allowing to the young patient to regain 6 months after her hospital admission a final visual acuity of 20/20 in her right eye. Conclusions and importance: The present case report suggests that the use of a rapid multiplex PCR strategy may result in a decrease of the mean hospital stage duration for severe infectious keratitis and in an improvement of the clinical outcome of severe keratitis infections. Nevertheless, additional prospective studies are needed to evaluate whether this innovative strategy may replace the current standard approach and optimize the therapeutic management of severe corneal infections.

Severe Primary Open-Angle Glaucoma and Agricultural Profession: A Retrospective Cohort Study.

While exposure to pesticides is a known risk factor for neurodegenerative brain diseases, little is known about the influence of environment on glaucoma neuropathy. We aimed to determine whether farmers are at higher risk of developing severe primary open-angle glaucoma (POAG). This retrospective cohort study (tertiary referral center, Reims University Hospital, France) included patients diagnosed with POAG in the last two years. Univariate analysis and adjusted multivariate logistic regression were performed to evaluate the association between agricultural profession and all recorded data. Glaucoma severity (primary outcome) and the number of patients who underwent filtering surgery (secondary outcome) were analyzed. In total, 2065 records were screened, and 772 patients were included (66 in the farmer group and 706 in the nonfarmer group). The risk of severe glaucoma was higher in the farmer group (adjusted odds ratio (aOR) 1.87, p = 0.03). More patients underwent filtering surgery in the farmer group in univariate analysis (p = 0.02) but with no statistical significance after adjustment (p = 0.08). These results suggest pesticide exposure may be a factor accelerating the neurodegeneration in POAG, although a direct link between the agricultural profession and the disease requires further extended studies to be demonstrated.

New model to better diagnose dry eye disease integrating OCT corneal epithelial mapping.

PURPOSE: To optimise the objective diagnosis of dry eye disease (DED), the capabilities of wide corneal epithelial mapping using optical coherence tomography (OCT) were studied and subsequently integrated into a new scoring method. METHODS: Fifty-nine patients (118 eyes) with DED and 55 control subjects (110 eyes) were included. All patients underwent a complete ocular surface evaluation. Corneal epithelial thickness was collected using OCT for seven zones. DED and the control group were compared using a t-test, and univariate receiver operating characteristic (ROC) curves were calculated to define the diagnostic ability of OCT epithelial mapping. Multivariate analyses were performed using artificial intelligence (random forest) and logistic regression approaches to define the best way to integrate OCT mapping in the diagnosis of DED. Then, a final multivariable model for diagnosing DED was validated through a bootstrapping method. RESULTS: The DED group had significant epithelial thinning compared with the controls, regardless of location. Superior intermediate epithelial thickness was the best marker for diagnosing DED using OCT (binormal estimated area under ROC: 0.87; best cut-off value: 50 µm thickness). The difference between the inferior and superior peripheral zones was the best marker for grading the severity of DED (analysis of variance, p=0.009). A multivariate approach identified other significant covariables which were integrated into a multivariate model to improve the sensitivity (86.4%) and specificity (91.7%) of this innovative diagnostic method. CONCLUSION: Including OCT corneal epithelial mapping in a new diagnostic tool for DED could allow optimisation of the screening and staging of the disease in current practice as well as for clinical research purposes.

Comparative Evaluation of Two SD-OCT Macular Parameters (GCC, GCL) and RNFL in Chiasmal Compression.

Purpose: To evaluate the relationship between different macular thickness parameters analyzed by SD-OCT and the central visual field (VF) evaluated with automated kinetic perimetry in a cohort of patients with pituitary tumors. Methods: Data from patients with pituitary adenoma treated at Reims University Hospital between October 1st, 2017, and May 31st, 2018 were collected. All patients underwent an automated kinetic perimetry and a SD-OCT to map the ganglion cell complex (GCC), the ganglion cell layer (GCL) thickness and the retinal nerve fiber layer (RNFL) using devices from two different manufacturers. Univariate and multivariate analysis were used to evaluate the correlation between the area of central VF in square degrees (deg2) and the SD-OCT parameters (µm). Results: Eighty-eight eyes were included in the analysis. All the thickness parameters measured in SD-OCT decreased with the visual field alteration. The best correlation was observed between superior thickness parameters (GCC, GCL) and the inferior central visual field. The most pertinent predictive factors for visual field loss were the inferior central GCL and the nasal RNFL (both AUC=0.775) with a sensitivity respectively of 86% and 70%. Conclusion: This study suggests that both GCC, GCL thickness parameters could be reliable predictors of central visual field impairment in patients with pituitary tumors. There was no significative difference between both devices.

Corneal in vivo confocal microscopy to detect belantamab mafodotin-induced ocular toxicity early and adjust the dose accordingly: a case report.

BACKGROUND: New targeted antibody-drug conjugates (ADCs) against multiple myeloma are known to induce adverse effects that may lead to treatment discontinuation. Preclinical studies reported early severe ocular damage related to the use of belantamab mafodotin (belamaf), including ocular surface inflammation, severe dry eye, and a specific toxicity to the cornea, namely microcystic keratopathy. While belamaf-induced ocular changes have not been prospectively studied, a better understanding of mechanisms involved as well as kinetics may aid in anticipating dose adjustment rather than stopping the treatment once clinical ocular damage is too severe. CASE PRESENTATION: A 61-year-old woman scheduled for belamaf as a fifth-line treatment against multiple myeloma was prospectively included. Clinical examinations were performed before and every 3 weeks afterward, together with in vivo confocal microscopy (IVCM) of the cornea. Visual acuity, symptoms, slit-lamp examination, and ultrastructural changes of the cornea were recorded according to the received dose of belamaf. More precisely, kinetics, shape, density, and location of the toxic corneal lesions have been followed and analyzed using IVCM. Also, specific lesions at the sub-basal nerve plexus layer were detected and characterized for the first time. This advanced approach allowed a better understanding of the belamaf-induced toxicity, further balancing the dose to maintain good vision and eye health while continuing the treatment. CONCLUSIONS: Systematic ultrastructural analysis and follow-up of the corneal state during ADCs treatment for multiple myeloma may open new avenues in the therapeutic approach. Early preclinical detection of ocular damage may accurately contribute to finding the correct dose for each patient and not stopping the treatment due to severe ocular adverse effects.

Implication of Melanopsin and Trigeminal Neural Pathways in Blue Light Photosensitivity in vivo.

Photophobia may arise from various causes and frequently accompanies numerous ocular diseases. In modern highly illuminated world, complaints about greater photosensitivity to blue light increasingly appear. However, the pathophysiology of photophobia is still debated. In the present work, we investigated in vivo the role of various neural pathways potentially implicated in blue-light aversion. Moreover, we studied the light-induced neuroinflammatory processes on the ocular surface and in the trigeminal pathways. Adult male C57BL/6J mice were exposed either to blue (400-500 nm) or to yellow (530-710 nm) LED light (3 h, 6 mW/cm2). Photosensitivity was measured as the time spent in dark or illuminated parts of the cage. Pharmacological treatments were applied: topical instillation of atropine, pilocarpine or oxybuprocaine, intravitreal injection of lidocaine, norepinephrine or "blocker" of the visual photoreceptor transmission, and intraperitoneal injection of a melanopsin antagonist. Clinical evaluations (ocular surface state, corneal mechanical sensitivity and tear quantity) were performed directly after exposure to light and after 3 days of recovery in standard light conditions. Trigeminal ganglia (TGs), brainstems and retinas were dissected out and conditioned for analyses. Mice demonstrated strong aversion to blue but not to yellow light. The only drug that significantly decreased the blue-light aversion was the intraperitoneally injected melanopsin antagonist. After blue-light exposure, dry-eye-related inflammatory signs were observed, notably after 3 days of recovery. In the retina, we observed the increased immunoreactivity for GFAP, ATF3, and Iba1; these data were corroborated by RT-qPCR. Moreover, retinal visual and non-visual photopigments distribution was altered. In the trigeminal pathway, we detected the increased mRNA expression of cFOS and ATF3 as well as alterations in cytokines' levels. Thus, the wavelength-dependent light aversion was mainly mediated by melanopsin-containing cells, most likely in the retina. Other potential pathways of light reception were also discussed. The phototoxic message was transmitted to the trigeminal system, inducing both inflammation at the ocular surface and stress in the retina. Further investigations of retina-TG connections are needed.

Very-high-frequency ultrasound corneal imaging as a new tool for early diagnosis of ocular surface toxicity in rabbits treated with a preserved glaucoma drug.

AIM: To evaluate very-high-frequency (VHF) ultrasound imaging as a new method to detect and quantify early corneal epithelium changes induced by chronic exposure to a benzalkonium-chloride-containing antiglaucoma drug. METHODS: Timolol preserved with 0.01% benzalkonium chloride solution was applied b.i.d. in 1 eye of 10 rabbits for 56 days. Unpreserved timolol solution was used as control. Ocular surface changes were assessed weekly combining clinical examinations, in vivo 60-MHz ultrasound imaging and ex vivo histological analysis. RESULTS: VHF ultrasound imaging allowed quantitative measurement of corneal epithelium thickness and qualitative imaging of toxic epithelial damage. It revealed significantly decreased epithelial thickness in vivo as early as the 21st day of treatment (40.75 +/- 1.72 microm at D0 vs. 39 +/- 2 at D21, vs. 31.9 +/- 2.98 at D56; p = 0.017 and p = 0.005, respectively). The first clinical changes appeared from the 42nd day of treatment (conjunctival redness, conjunctival staining and corneal staining; D56 compared to D0: p = 0.005, 0.01 and 0.004, respectively) and then correlated with VHF ultrasound data. Epithelial thickness measured with VHF ultrasound was correlated with histological epithelial pachymetry (p < 0.001) and with the corneal damage score assessed with scanning electron microscopy (p = 0.038). CONCLUSION: VHF ultrasound imaging provided an early in vivo diagnosis of corneal epithelium pathology induced by chronic exposure to a preserved glaucoma drug, before the first clinical evidence of ocular toxicity. It could be a new reproducible method to detect the toxicity of glaucoma medication so that therapy can then be adapted.

Early recovery of quality of vision and optical performance after refractive surgery: Small-incision lenticule extraction versus laser in situ keratomileusis.

PURPOSE: To assess the early time course of the visual function after small-incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). SETTING: Quinze-Vingts National Ophthalmology Hospital, Paris, France. DESIGN: Prospective case series. METHODS: Patients scheduled for bilateral small-incision lenticule extraction or LASIK were consecutively enrolled. In addition to standard refraction and visual acuity, contrast sensitivity, aberrometry, and patient-reported quality of vision and overall satisfaction were measured 1 day, 7 days, and 1 month postoperatively. RESULTS: Each group comprised 23 patients (46 eyes). The postoperative contrast sensitivity was better in the LASIK group at 1 day (P = .014) and 7 days (P = .001) but not at 1 month. No significant differences in visual acuity, efficacy, or safety were found between the 2 groups throughout the follow-up. The objective scatter index assessed by double-pass aberrometry was better after LASIK 1 day postoperatively (P = .036) but was not statistically different thereafter. The patient-reported quality of vision was significantly worse in the small-incision lenticule extraction group than in the LASIK group at 7 days (P = .010). Global satisfaction did not differ between groups throughout the study. Significant correlations were found between contrast sensitivity and aberrometry in both groups at all examinations. CONCLUSIONS: Targeted analysis of early quality of vision through objective and subjective methods suggested that compared with LASIK, a slight delay in corneal optical recovery after small-incision lenticule extraction might lead to reduced contrast sensitivity and specific patient-reported visual disturbance during the first postoperative week with no effect on overall patient satisfaction.

Blue light phototoxicity toward human corneal and conjunctival epithelial cells in basal and hyperosmolar conditions.

AIMS: The ocular surface is the very first barrier between the visual system and external environment. It protects the eye from the exposure to various light sources that significantly emit in blue spectrum. However, the impact of blue light on the ocular surface has been poorly explored so far. In this study, we investigated in vitro the phototoxicity of blue light illumination in human epithelial cells of the ocular surface. We worked either in basal conditions or under hyperosmolar stress, in order to mimic dry eye disease (DED) that is the most common disease involving the ocular surface. RESULTS: Corneal and conjunctival epithelial cells suffered the most from violet-blue light but also from longer-wave blue light. Exposure to blue wavebands significantly decreased cellular viability, impacted on cellular morphology and provoked reactive oxygen species (ROS) over-production. Conjunctival epithelial cell line had a greater photosensitivity than the corneal epithelial one. Hyperosmolar stress potentiated the blue light phototoxicity, increasing inflammation, altering mitochondrial membrane potential, and triggering the glutathione-based antioxidant system. INNOVATION: In human epithelial corneal and conjunctival cells of the ocular surface, we demonstrated the harmful impact of blue light on viability, redox state and inflammation processes, which was modified by hyperosmolarity. CONCLUSION: Blue light induced cell death and significant ROS production, and altered the expression of inflammatory genes and operation of the cellular defensive system. We established for the first time that hyperosmolar stress impacted phototoxicity, further suggesting that DED patients might be more sensitive to blue light ocular toxicity.

Quality of vision after cataract surgery after Tecnis Z9000 intraocular lens implantation: effect of contrast sensitivity and wavefront aberration improvements on the quality of daily vision.

PURPOSE: To compare ocular performance and quality of vision in pseudophakic eyes with an aspherical intraocular lens (IOL) or a conventional spherical IOL. SETTING: Bretonneau University Hospital, Tours, France. METHODS: Twenty patients (40 eyes) were randomly divided in 2 equal groups to bilaterally receive the aspherical Tecnis Z9000 IOL (AMO) or the spherical CeeOn Edge 911 IOL (AMO). Contrast sensitivity was measured and ocular wavefront analysis performed before surgery and 6 months after. Patients completed the Activities of Daily Vision Scale (ADVS) to evaluate patient-centered visual outcomes. Other examinations included refraction before and after mydriasis and pupil diameter. RESULTS: The mean postoperative best corrected visual acuity (logMAR) was 0.03 +/- 0.05 (SD) in the Tecnis group and 0.01 +/- 0.05 in the CeeOn Edge group (P = .41). Refractive evaluation with mydriasis showed a mean myopic shift as low as -0.02 +/- 0.36 diopter (D) in the Tecnis group and -0.51 +/- 0.37 D in the CeeOn Edge group (P = .001). Mesopic contrast sensitivity at high spatial frequencies was significantly better in the Tecnis group (P<.001), while contrast sensitivity under photopic and glare conditions was not different between the 2 groups. Spherical aberration was significantly lower in the Tecnis group, which had a mean Z(4)(0) of 0.01 +/- 0.06 microm, than in the CeeOn Edge group, which had a mean Z(4)(0) of 0.16 +/- 0.12 microm (P<.001). The global score on the ADVS was not statistically different between groups; however, quality of distance vision was better in the Tecnis group than in the CeeOn Edge group (mean 99.0 +/- 2.0 versus 89.2 +/- 3.4) (P<.001). CONCLUSION: Implantation of an aspherical IOL with a negative spherical aberration resulted in reduced ocular spherical aberration and improved mesopic contrast sensitivity and led to better subjective quality of vision.

The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.

Purpose: Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Method: Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Results: Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 µM) and O2 consumption (IC50, 10.9 µM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 µM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 µM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 µM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Conclusions: Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.

In vivo confocal microscopy as a novel and reliable tool for the diagnosis of Demodex eyelid infestation.

AIMS: Demodex mites are implicated in several ocular surface diseases such as blepharitis, ocular rosacea and dry eye syndrome. Demodex eyelid infestation is classically diagnosed by analysing depilated eyelashes under the light microscope. The use of in vivo confocal microscopy (IVCM) could be an easy way to improve its diagnosis. The ability of IVCM to identify Demodex was evaluated and compared with the classic depilation method. METHODS: Eight healthy subjects, 22 patients with dry eye syndrome without anterior blepharitis and 18 patients with anterior blepharitis were examined using lower eyelid IVCM (lash follicles and meibomian glands (MGs)). Twenty-five of the 48 subjects underwent both an IVCM examination and classic depilation to compare the two methods. Ex vivo Demodex obtained from lash depilation were also analysed using the confocal microscope. RESULTS: IVCM found 100% of the mite infestations among patients with anterior blepharitis, 60% among dry eye patients without blepharitis and 12% in healthy subjects, whereas the depilation technique found 100%, 50% and 0%, respectively. Demodex brevis and Demodex larvae inside the lash follicles were better detected by IVCM. In symptomatic patients, the Demodex infestation was often associated with MG dysfunction, which was better characterised using IVCM in symptomatic patients (60% and 40% of meibomianitis and gland fibrosis, respectively). CONCLUSIONS: IVCM is an efficient and reliable tool for the diagnosis of eyelid mite infestation and may also provide an evaluation of MGs.