Inflammation of Dry Eye Syndrome: A Cellular Study of the Epithelial and Macrophagic Involvement of NFAT5 and RAGE.

Dry eye inflammation is a key step in a vicious circle and needs to be better understood in order to break it. The goals of this work were to, first, characterize alarmins and cytokines released by ocular surface cells in the hyperosmolar context and, second, study the role of NFAT5 in this process. Finally, we studied the potential action of these alarmins in ocular surface epithelial cells and macrophages via RAGE pathways. HCE and WKD cell lines were cultured in a NaCl-hyperosmolar medium and the expression of alarmins (S100A4, S100A8, S100A9, and HMGB1), cytokines (IL6, IL8, TNFα, and MCP1), and NFAT5 were assessed using RT-qPCR, ELISA and multiplex, Western blot, immunofluorescence, and luciferase assays. In selected experiments, an inhibitor of RAGE (RAP) or NFAT5 siRNAs were added before the hyperosmolar stimulations. HCE and WKD cells or macrophages were treated with recombinant proteins of alarmins (with or without RAP) and analyzed for cytokine expression and chemotaxis, respectively. Hyperosmolarity induced epithelial cell inflammation depending on cell type. NFAT5, but not RAGE or alarmins, participated in triggering epithelial inflammation. Furthermore, the release of alarmins induced macrophage migration through RAGE. These in vitro results suggest that NFAT5 and RAGE have a role in dry eye inflammation.

Efficacy of treatments for neurotrophic keratopathy: a systematic review and meta-analysis.

PURPOSE: Management of NK can be difficult, involving a range of treatments with variable efficacy. We conducted a systematic review and meta-analysis to evaluate the efficacy of medical and surgical treatments for neurotrophic keratitis (NK). METHOD: PubMed, Cochrane Library, Embase, ClinicalTrial.gov, and ScienceDirect were searched for studies assessing efficacy of NK treatments. We computed random-effect meta-analyses on corneal healing, time to complete healing, and visual acuity changes between baselines and after treatment, stratified on treatment classes. We followed the PRISMA guidelines (registration number CRD42021225721). RESULTS: We included 20 studies: 571 patients and 5 treatment classes (2 surgical and 3 non-surgical). The percentage of patients with complete corneal healing did not differ between specific treatments (nerve growth factor eyedrops (NGF), 75%, 95CI 46 to 104%; autologous serum (AS), 92%, 86 to 98%; neurotization, 99%, 95 to 103%; amniotic membrane transplantation (AMT), 86%, 78 to 94%). All specific treatments had better percentage of complete healing (p < 0.001) than non-specific treatment groups, i.e., mainly lubricants (23%, 14 to 32). Time to complete healing was 24.2 days (5.4 to 43.1) with NGF, 27.6 days (15.2 to 40.0) with AS, 117 days (28.8 to 205.2) with neurotization, and 16.4 days (11.1 to 21.7) with AMT. Only NGF and AMT improved visual acuity. Efficacy outcomes were not affected by sociodemographic (age, sex) nor severity of disease (Mackie stages). CONCLUSION: We confirmed the efficacy of specific treatments in NK. Further comparative trials are needed to investigate the medical and economic benefits of innovative therapies.

Benefits of using corneal topography to choose subjective refraction technique in keratoconus (RE-CON): a prospective comparative crossover clinical study.

PURPOSE: In prospective no-masking, comparative, crossover monocenter clinical trial, we aimed to evaluate whether the optimal subjective refraction technique varies with the keratoconus topography and to identify relevant topographic criteria. METHOD: This study included 72 keratoconus eyes with impaired visual acuity. Each eye tested three methods of refraction (Jackson cylinder, astigmatism dial, stenopeic slit), resulting in three eyeglass lenses. Patients were assigned to the group corresponding to the eyeglass lens offering the best visual acuity. Five topographical characteristics were collected via the Pentacam: mean keratometry (Km), maximum keratometry (Kmax), distance from corneal center to Kmax (dKmax), Belin/Ambrosio Display (BAD_D), and index of surface variance (ISV). RESULTS: Forty-six eyes were included in the dial group (64.8%), 23 eyes in the cylinder group (32.4%), and only 2 eyes in the slit group (2.8%); thus, we only compared dial and cylinder groups. The main analysis retrieved a significant probability to choose dial technic for BAD_D (p = 0.024); when BAD_D is > 9.71 (ROC threshold), the positive predictive value (PPV) = 89.5%, and for ISV, p = 0.012; when ISV is > 77, PPV = 89.1%. The sub-analysis of patients with different visual acuities between cylinder and dial confirmed these results with slightly different thresholds: the probability to choose dial technic was for BAD_D, p = 0.03; when BAD_D is > 7.55, PPV = 90%, and for ISV, p = 0.0084; when ISV is > 71, PPV = 88.5%. CONCLUSION: Refraction method is linked to topographic indices ISV and BAD_D. A BAD_D > 7.55 indicates the dial method. In addition to keratoconus screening and diagnosis, this study suggests a new application of the topographer to select a suitable refraction method for eyeglass prescription. TRIAL REGISTRATION: Study registered on the ClinicalTrials.gov database under n°: NCT04174209.

Efficacy of medical treatments for vernal keratoconjunctivitis: A systematic review and meta-analysis.

BACKGROUND: Vernal keratoconjunctivitis (VKC) is a severe type of allergic conjunctivitis for which treatment strategies are still under debate. OBJECTIVES: This study sought to conduct a systematic review and meta-analysis to evaluate the efficacy of medical treatments for VKC. METHODS: The PubMed, Cochrane Library, Embase, and ScienceDirect databases were searched to assess the efficacy of treatments for VKC. Random-effect meta-analyses on changes in clinical scores of symptoms and signs between baseline and after treatment, stratified on treatment classes, were computed. Meta-regressions were searched for potential influencing parameters. RESULTS: Included were 45 studies (27 randomized controlled trials and 18 prospective cohort studies), 1749 patients (78% were men; mean age, 11.2 years), and 12 different treatment classes. Mast cell stabilizers (MCSs; usually considered as first-line therapy), cyclosporine, and tacrolimus were the most studied drugs (in three-quarters of studies). Overall, all clinical scores improved. Total symptom and sign score decreased for MCSs (effect size, -3.19; 95% CI, -4.26 to -2.13), cyclosporine (effect size, -2.06; 95% CI, -2.72 to -1.40), and tacrolimus (effect size, -2.39; 95% CI, -3.36 to -1.43). No significant differences were shown depending on treatment classes, concentration, age, sex, baseline activity scores, and atopy. Sensitivity analyses demonstrated similar results. CONCLUSIONS: This study confirms the efficacy of MCSs in the treatment of VKC. Efficacy of cyclosporine and tacrolimus did not differ, suggesting that tacrolimus is a good alternative to cyclosporine for severe cases of VKC. Further studies are needed to compare other drugs and their precise place in treatment strategy.

Deep learning versus ophthalmologists for screening for glaucoma on fundus examination: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to compare deep learning versus ophthalmologists in glaucoma diagnosis on fundus examinations. METHOD: PubMed, Cochrane, Embase, ClinicalTrials.gov and ScienceDirect databases were searched for studies reporting a comparison between the glaucoma diagnosis performance of deep learning and ophthalmologists on fundus examinations on the same datasets, until 10 December 2020. Studies had to report an area under the receiver operating characteristics (AUC) with SD or enough data to generate one. RESULTS: We included six studies in our meta-analysis. There was no difference in AUC between ophthalmologists (AUC = 82.0, 95% confidence intervals [CI] 65.4-98.6) and deep learning (97.0, 89.4-104.5). There was also no difference using several pessimistic and optimistic variants of our meta-analysis: the best (82.2, 60.0-104.3) or worst (77.7, 53.1-102.3) ophthalmologists versus the best (97.1, 89.5-104.7) or worst (97.1, 88.5-105.6) deep learning of each study. We did not retrieve any factors influencing those results. CONCLUSION: Deep learning had similar performance compared to ophthalmologists in glaucoma diagnosis from fundus examinations. Further studies should evaluate deep learning in clinical situations.

Irregular Astigmatism Management Using SPOT Scleral Lenses in the Treatment of Corneal Ectasia and Penetrating Keratoplasty.

PURPOSE: To evaluate the outcome of SPOT scleral lenses in the management of irregular astigmatism in patients with corneal ectasia and penetrating keratoplasty. Second, we analyzed patients' characteristics and tolerance, comfort, and geometries of fitted lenses. METHOD: Over a 5-year period, we included patients experiencing irregular astigmatism fitted with SPOT scleral contact lenses, from the University Hospital of Clermont-Ferrand, France. Data collected included corneal diseases, refractive error, best-corrected visual acuity (VA) with SPOT lenses, geometry of the lens, number of adjustment consultations, and the duration of follow-up. Comfort, quality of vision, less handling, and satisfaction were evaluated using visual analog scales after a 6-month follow-up period. RESULTS: Sixty-five patients were included, analyzing 107 eyes. Eighty percent of patients still daily wore lenses after a follow-up of 22.3±13.8 months. Visual acuity improved by 0.47±0.51 logarithm of the minimum angle of resolution (average increase of 5 lines) (P<0.001) after wearing scleral lenses. Comfort, quality of vision, less handling, and satisfaction of contact lenses were excellent (>75/100). Contact lenses were daily worn 10.0±4.1 hr/day. Most patients wore size M (17 mm) lenses (53.3% of patients), with an average sagittal height of 5.2±1.2 mm. Internal toricity was used in 30% of cases. Best geometry was found after 2.69±0.87 consultations. CONCLUSION: SPOT scleral contact lenses are an effective and well tolerated method to improve the VA of patients with irregular astigmatism.

Safety and efficacy of a standardized intracameral combination of mydriatics and anesthetic for cataract surgery in type-2 diabetic patients.

BACKGROUND: Cataract surgery in diabetics is more technically challenging due to a number of factors including poor intraoperative pupil dilation and a higher risk of vision threatening complications. This study evaluates the safety and efficacy of an intracameral combination of 2 mydriatics and 1 anesthetic (ICMA, Mydrane) for cataract surgery in patients with well-controlled type-2 diabetes. METHODS: Post-hoc subgroup analysis of a phase 3 randomized study, comparing ICMA to a conventional topical regimen. Data were collected from 68 centers in Europe and Algeria. Only well-controlled type-2 diabetics, free of pre-proliferative retinopathy, were included. The results for non-diabetics are also reported. The primary efficacy variable was successful capsulorhexis without additional mydriatic treatment. Postoperative safety included adverse events, endothelial cell density and vision. RESULTS: Among 591 randomized patients, 57 (9.6%) had controlled type 2 diabetes [24 (42.1%) in the ICMA Group and 33 (57.9%) in the Topical Group; intention-to-treat (ITT) set]. Among diabetics, capsulorhexis was successfully performed without additional mydriatics in 24 (96.0%; modified-ITT set) patients in the ICMA Group and 26 (89.7%) in the Topical Group. These proportions were similar in non-diabetics. No diabetic patient [1 (0.5%) non-diabetics] in the ICMA Group had a significant decrease in pupil size (≥3 mm) intraoperatively compared to 4 (16.0%; modified-ITT set) diabetics [16 (7.3%) non-diabetics] in the Topical group. Ocular AE among diabetics occurred in 2 (8.0%; Safety set) patients in the ICMA Group and 5 (16.7%) in the Topical Group. Endothelial cell density at 1 month postoperatively was similar between groups in diabetics (P = 0.627) and non-diabetics (P = 0.368). CONCLUSIONS: ICMA is effective and can be safely used in patients with well-controlled diabetes, with potential advantages compared to a topical regimen including reduced systemic risk, better corneal integrity and reduced risk of ocular complications. TRIAL REGISTRATION: The trial was registered at (reference # NCT02101359) on April 2, 2014.

Investigation of antioxidant systems in human meibomian gland and conjunctival tissues.

Oxidative stress (OS) associated with direct contact with the environment and light exposure is a very potent and continuous stressor of the ocular surface and internal structures of the eye that are required to manage its effects. Constant replenishment of tears together with the superficial lipid layer produced by the meibomian glands (MG) is one protective mechanism. The lipid-rich fraction of the tears coats the deeper aqueous fraction, preventing its evaporation. However, lipids are particularly sensitive to oxidative damage that could alter tear film quality. To counteract oxidative damage, MG along with other structures of the ocular surface use primary antioxidant (AO) systems to limit OS damage such as lipid peroxidation. Limited information concerning the primary enzymatic AO system of the human MG prompted this investigation. Using different approaches (RT-PCR, enzymatic activity assays and immuno-fluorescent microscopy), we determined the presence, distribution and subcellular locations of the major AO enzymes belonging to the classical catalytic triad (superoxide dismutase, catalase and glutathione peroxidases) in adult human MG and conjunctiva (Conj). We showed that both tissues exhibit glutathione peroxidase expression. In addition to the ubiquitous cytosolic GPx1 protein, there was significant expression of GPx2, GPx4 and GPx7. These isoforms are known to preferentially scavenge phospholipid-hydroperoxide compounds. This characterization of the primary AO system of human MG and Conj may help pave the way for the development of diagnostic procedures and have implications for treatment of common MG dysfunction (MGD) and dry eye syndrome (DES).

Myocilin expression is regulated by retinoic acid in the trabecular meshwork-derived cellular environment.

Glaucoma is the leading cause of irreversible blindness and is usually classified as angle closure and open angle glaucoma (OAG). Primary open angle glaucoma represents the most frequent clinical presentation leading to ganglion cell death and optic nerve degeneration as a main consequence of an intraocular pressure' (IOP) increase. The mechanisms of this IOP increase in such pathology remain unclear but one protein called Myocilin could be a part of the puzzle in the trabecular meshwork (TM). Previously described to be transcriptionally regulated by glucocorticoids, the comprehension of the trabecular regulation of Myocilin' expression has only weakly progressed since 15 years. Due to the essential molecular and cellular implications of retinoids' pathway in eye development and physiology, we investigate the potential role of the retinoic acid in such regulation and expression. This study demonstrates that the global retinoids signaling machinery is present in immortalized TM cells and that Myocilin (MYOC) expression is upregulated by retinoic acid alone or combined with a glucocorticoid co-treatment. This regulation by retinoic acid acts through the MYOC promoter which contains a critical cluster of four retinoic acid responsive elements (RAREs), with the RARE-DR2 presenting the strongest effect and binding the RARα/RXRα heterodimer. All together, these results open up new perspectives for the molecular understanding glaucoma pathophysiology and provide further actionable clues on Myocilin gene regulation.

Safety of an Intracameral Fixed Combination for Mydriasis and Intraocular Anaesthesia During Cataract Surgery.

Purpose: To compare the safety of a standardized, commercially available intracameral combination of mydriatics and anesthetic (ICMA) with a reference topical mydriatic regimen for cataract surgery. Patients and Methods: The safety results from two international, randomized, controlled clinical studies were combined to compare ICMA at the beginning of cataract surgery (ICMA group) to the reference topical mydriatic regimen (reference group). Data were collected on ocular and systemic adverse events, corneal and anterior chamber examination, endothelial cell density, retinal thickness and visual acuity. Analysis was performed on a pooled safety set from both studies, preoperatively and up to 1 month postoperatively. Results: 342 patients received ICMA and 318 the reference topical regimen. Ocular adverse events were reported in 17.0% of patients in the ICMA group and 18.6% in the reference group. No difference was shown between groups in endothelial cell density (2208 ± 498 cells/mm2 for ICMA group versus 2241 ± 513 cells/mm2 for the reference group; p=0.547) and retinal thickness (change from baseline less than 50 µm in 94.7% versus 95.0% of patients, respectively) at 1 month postoperatively. At 1-day post-surgery, less patients in the ICMA group had moderate or severe (Grades 2 and 3) superficial punctate corneal staining (3.9% versus 7.0% for the reference group; p=0.064). Postoperatively, some ocular symptoms were also less frequently reported in the ICMA group. Best-corrected visual acuity increased in 96.0% of patients in the ICMA group and 95.8% in the reference group at 1 month. Conclusion: ICMA injection at the beginning of cataract surgery was demonstrated to be safe and may also provide perioperative and postoperative advantages over the standard topical mydriatic regimen.

Multiple Sclerosis-Associated Uveitis: A Case Report of Refractory Bilateral Chronic Granulomatous Panuveitis Successfully Treated with Tocilizumab.

PURPOSE: To report a case of uveitis associated with multiple sclerosis (MS) that was refractory to multiple lines of therapy but achieved remission with tocilizumab. METHODS: We conducted a retrospective analysis of the patient's medical record including clinical, biological and imaging data. RESULTS: A 33-year-old female patient with a history of MS inactive for 5 years on teriflunomide, and no significant medical or ophthalmological history, presented with bilateral granulomatous panuveitis. Initial examination revealed a visual acuity of 0.4 logMAR and 1.3 logMAR in the right eye and the left eye, respectively, along with a significant anterior chamber flare in both eyes, posterior synechiae, large granulomatous keratic precipitates, bilateral vitritis, bilateral macular edema with foveolar pigment epithelial detachment, and significant bilateral venous and arterial vasculitis. The patient underwent several lines of treatment, all of which proved unsuccessful, including corticosteroids alone or in combination with azathioprine, methotrexate, and mycophenolate mofetil. As a final therapeutic option, tocilizumab was initiated, leading to the remission of uveitis. One year later, the uveitis remained inactive under a 5 mg/day prednisone regimen. CONCLUSIONS: Tocilizumab appears to be an efficient option for managing uveitis associated with MS and may be a valuable choice for clinicians dealing with such cases.

Efficacy of artificial tears containing trehalose and hyaluronic acid for dry eye disease in women aged 42-54 versus ≥ 55 years.

BACKGROUND AND OBJECTIVES: Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and hyaluronic acid (HA) in women aged 42-54 years (mixed-hormonal status) versus ≥ 55 years (postmenopausal) and with moderate and severe DED. METHODS: This was a post-hoc analysis of three clinical trials assessing the efficacy of artificial tears containing trehalose (3%) and HA (0.15%) in women with an Ocular Surface Disease Index (OSDI) ≥ 18. Patients instilled one drop of the artificial tears in each eye 3 to 6 times daily and were evaluated at baseline and after 84 ± 7 days for DED symptom severity (OSDI), hyperemia (McMonnies scale), tear break-up time (TBUT), corneal and conjunctival staining (Oxford and Van Bjisterveld scales), tear production (Schirmer I test), and ocular symptoms. RESULTS: A total of 273 women were evaluated, 61 of age 42-54 years; 212 of ≥ 55 years. DED symptoms, as measured by the OSDI, decreased significantly with the treatment in both age groups (p < 0.0001). Conjunctival hyperemia decreased significantly and TBUT increased significantly in both groups, especially in women of age 42-54 (both p < 0.0001). The global (corneal and conjunctival) staining score decreased significantly in both groups, but also more in women of age 42-54 years. No differences were observed between age groups for any of the variables measured, except for visual acuity. DED symptoms were consistently reported more frequently by the mixed hormonal status women, but also the effect of the treatment was more pronounced in this group. CONCLUSIONS: Artificial tears with trehalose and HA significantly improved the symptoms of DED in women aged 42-54 and ≥ 55 years. The decrease in symptoms was more pronounced in women of age 42-54 years, suggesting better mechanisms of recovery from inflammation and loss of ocular surface homeostasis.

Myopia and Near Work: A Systematic Review and Meta-Analysis.

BACKGROUND: Myopia is a global public health problem affecting quality of life and work productivity. Data is scarce regarding the effects of near work on myopia. Providing a larger meta-analysis with life-long perspective, including adults and occupational exposure seemed needed. METHODS: We searched PubMed, Cochrane Library, Embase and Science Direct for studies reporting myopia prevalence in near work. Myopia was defined as a mean spherical equivalent ≤ -0.50 diopter. We performed a meta-analysis using random-effects model on myopia prevalence, myopia progression per year, and odds ratio (OR) of myopia in near work, completed by subgroup analyses and meta-regressions on patients' characteristics, type of work in adults, geographic zones, time and characteristics of near work. RESULTS: We included 78 studies, representing a total of 254,037 participants, aged from 6 to 39 years. The global prevalence of myopia in near work was 35% (95% CI: 30 to 41%), with a prevalence of 31% (95% CI: 26 to 37%) in children and 46% (95% CI: 30 to 62%) in adults. Myopia progression was -0.39 diopters per year (-0.53 to -0.24 D/year), ranging from -0.44 (-0.57 to -0.31) in children to -0.25 D/year (-0.56 to 0.06) in adults. The odds of myopia in workers exposed vs. non-exposed to near work were increased by 26% (18 to 34%), by 31% (21 to 42%) in children and 21% (6 to 35%) in adults. Prevalence of myopia was higher in adults compared to children (Coefficient 0.15, 95% CI: 0.03 to 0.27). CONCLUSIONS: Near work conditions, including occupational exposure in adults, could be associated with myopia. Targeted prevention should be implemented in the workplace.

Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches.

Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of PAX6-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated. Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the PAX6 gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options. Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.

Keratoconus and the Impact of Treatment on Patients' Quality of Life: A Qualitative Study.

INTRODUCTION: Keratoconus has a significant impact on patients' quality of life (QoL), from diagnosis to the advanced stages of the disease. The aim of this research was to identify domains of QoL affected by this disease and its treatment. METHODS: Phone interviews were conducted using a semi-structured interview guide, with patients with keratoconus stratified according to their current treatment. A board of keratoconus experts helped identify the guide's main themes. RESULTS: Thirty-five patients (rigid contact lenses, n = 9; cross-linking, n = 9; corneal ring implants, n = 8; and corneal transplantation, n = 9) were interviewed by qualitative researchers. Phone interviews revealed several QoL domains affected by the disease and its treatments: "psychological", "social life", "professional life", "financial costs" and "student life". All domains were impacted, independently of the treatment history. Few differences were found between treatment regimens and keratoconus stages. Qualitative analysis enabled the development of a conceptual framework based on Wilson and Cleary's model for patient outcomes common to all patients. This conceptual model describes the relationship between patients' characteristics, their symptoms, their environment, their functional visual impairment and the impact on their QoL. CONCLUSIONS: These qualitative findings supported the generation of a questionnaire to evaluate the impact of keratoconus and its treatment on patients' QoL. Cognitive debriefings confirmed its content validity. The questionnaire is applicable for all stages of keratoconus and treatments and may help tracking change over time in regular clinical settings. Psychometric validation is yet to be performed before its use in research and clinical practices.

Different Approach to Manage Demodex Blepharitis - Initial and Maintenance Treatment.

PURPOSE/AIM OF THE STUDY: To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes. MATERIALS AND METHODS: Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires. RESULTS: All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods. CONCLUSIONS: Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use.

Two-year longitudinal follow-up of visual illusions and hallucinations in Parkinson's disease.

BACKGROUND: Previous longitudinal studies assessing visual hallucinations in Parkinson's disease (PD) have not specifically considered the respective evolution of visual illusions (VI) and visual hallucinations (VH), neither did they assess the role of ocular pathology on the evolution of those manifestations. OBJECTIVE: We aimed to determine whether VI evolve towards VH along the time in PD, and whether ophthalmological treatment may have a positive effect on the prognosis of those visuo-perceptive manifestations. METHODS: PD patients from a previous cohort [PD with VI (n = 26), PD with VH (n = 28), and PD without VI or VH (n = 28)] were contacted by phone 2 years later and questioned regarding the current presence of VI or VH, any current visual complaints, and the occurrence of any ophthalmological or antipsychotic treatment during the 2-year period, as well as any dopatherapy adjustment. RESULTS: Among PD-VI patients, 43% normalized, 48% remained PD-VI, 9% evolved towards coexisting VI and VH, and none converted to pure VH. Among PD-VH patients, 42% normalized, 32% remained PD-VH, 21% evolved towards coexisting VI and VH, and only 5% converted to pure VI. At follow-up, visual complaints remained greater among PD-VI and PD-VH compared to controls (p = 0.005). Among PD-VI and PD-VH who became control at follow-up, 35% received ophthalmologic treatment, 29% antipsychotic treatment, and 23% a dopatherapy reduction. CONCLUSION: PD Patients with VI do not necessarily evolve towards VH over time, and ophthalmological treatment may have a positive effect on the prognosis of those visuo-perceptive manifestations in PD similar to antipsychotic treatment and dopatherapy adjustment. TRIAL REGISTRATION: clinicaltrials.gov number NCT01114321.