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Purpose: To report first clinical use of novel medical treatment for Acanthamoeba keratitis., Methods: Interventional observational case series. Two patients with Acanthamoeba keratitis were unsuccessfully treated with polihexanide (PHMB) 0.02% and propamidine 0.1% for 6 weeks, then all were shifted in a compassionate use of PHMB 0.08% with novel standardized protocol. The postinterventional follow-up of patients was at least 7 months., Results: PHMB 0.08% eyedrops in a novel standardized protocol improved infection resolution and led to complete healing of the lesion after 4 weeks in the two cases. Corneal opacities and neovascularization decreased slowly, best-corrected visual acuity slightly improved and progressively increased in the further 7 months, and no infection recurrence occurred., Conclusions: This preliminary report of two cases shows promising response to polihexanide 0.08% lowering drastically the illness duration, with reduced chance of recurrence, and mostly improving patients' quality of life., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Contact Lens Association of Opthalmologists.)

Purpose: The cataract surgery dissatisfaction rate is 20% to 35% due to ocular surface discomfort. We investigate the ocular surface discomfort after surgical failure as a consequence of age-related parainflammation. We also aim to prevent it by immune-modulating prophylactic management., Methods: Monocentric clinical trial realized in a teaching hospital. Prospective, randomized, open-label, unmasked clinical trial. One hundred patients diagnosed with cataracts underwent phacoemulsification surgery. Groups A (<65 years; n = 25) and B (>75 years; n = 25) received surgery only. Groups C and D (both >75 years and both n = 25) used cyclosporine A 0.1% cationic emulsion (CE) eye drops or CE lubricating eye drops (both twice daily), respectively, for 30 days before surgery. Patients were followed up 90 days after surgery. The primary outcome was postoperative ocular surface failure; secondary outcomes examined the influence of prophylactic cyclosporine A 0.1% CE therapy on ocular surface outcomes., Results: Group B demonstrated greater severity regarding ocular surface signs and symptoms throughout the study period, versus all other groups. Signs/symptoms were typically lower in Group A. Group C achieved significant reductions in conjunctival Symptom Assessment in Dry Eye values ( P < 0.05), conjunctival hyperemia severity ( P < 0.01), and meibomian gland dysfunction ( P < 0.001) at Day 45, versus Group B, and tear break-up time was increased ( P < 0.001). Ocular surface inflammatory marker transcription (HLADR, intercellular adhesion molecule 1 [ICAM-1], and interleukin 6 [IL-6]) was significantly downregulated in Group C, versus Group B, at 90 days ( P < 0.05)., Conclusions: Cataract surgery induced ocular surface system failure with a clinically significant persistent inflammatory status (InflammAging) in patients older than 75 years. Prophylactic cyclosporine A 0.1% CE eye drops were associated with improved ocular surface homeostasis and reductions in inflammatory markers., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dupilumab-associated ocular surface disease is a common clinical sign appearing in patients with atopic dermatitis (AD) just few months after dupilumab treatment start, developing in about 25% of patients. Atopic keratoconjunctivitis (AKC) is a well-identified clinical entity, defined as a chronic inflammatory disease of eye that affects 25%-40% of patients with AD. Most clinical signs of ocular involvement in AD patients treated with dupilumab overlaps the AKC symptoms and signs. We supposed that Dupilumab-associated ocular surface disease and AKC represent the same disease but differently called by dermatologists and ophthalmologists. AKC-like disease may develop during dupilumab therapy as a consequence of alternative cytokines pathway activation (e.g. IL33) secondary to IL-4/13 pathway block. The novel upadacitinib drug may bypass ILs pathway through Janus Kinases selective inhibition, avoiding positive or negative ILs feedback at the ocular surface level. In this case report, molecular analysis on conjunctival samples showed a lower ocular surface inflammation (lower expression of HLADR) although higher levels of IL4 and IL13 in a patient with AD and AKC during upadacitinib therapy, compared to prior dupilumab treatment. Target therapies in patients suffering from AD may prevent ocular and dermatological comorbidities improving quality of life before quality of skin and vision., Competing Interests: None to declare., (© 2024 The Authors. Skin Health and Disease published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Purpose: Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are common gastrointestinal disorders with extraesophageal manifestations (EGERD). Studies showed a correlation between GERD/LPR and ocular discomfort. Our aim was to report the prevalence of ocular involvement in patients with GERD/LPR, describe clinical and biomolecular manifestations, and provide a treatment strategy for this novel EGERD comorbidity., Methods: Fifty-three patients with LPR and 25 healthy controls were enrolled in this masked randomized controlled study. Fifteen naive patients with LPR were treated with magnesium alginate eye drops and oral therapy (magnesium alginate and simethicone tablets) with a 1-month follow-up. Clinical ocular surface evaluation, Ocular Surface Disease Index questionnaire, tear sampling, and conjunctival imprints were performed. Tear pepsin levels were quantified by ELISA. Imprints were processed for human leukocyte antigen-DR isotype (HLA-DR) immunodetection and for HLA-DR, IL8, mucin 5AC (MUC5AC), nicotine adenine dinucleotide phosphate (NADPH), vasoactive intestinal peptide (VIP), and neuropeptide Y (NPY) transcript expression (PCR)., Results: Patients with LPR had significantly increased Ocular Surface Disease Index ( P < 0.05), reduced T-BUT ( P < 0.05), and higher meibomian gland dysfunction ( P < 0.001) compared with controls. After treatment, tear break-up time (T-BUT) and meibomian gland dysfunction scores improved to normal values. Pepsin concentration increased in patients with EGERD ( P = 0.01) and decreased with topical treatment ( P = 0.0025), significantly. HLA-DR, IL8, and NADPH transcripts were significantly increased in the untreated versus controls and comparable significant values were obtained after treatment ( P < 0.05). MUC5AC expression significantly increased with treatment ( P = 0.005). VIP transcripts were significantly higher in EGERD than in controls and decreased with the topical treatment ( P < 0.05). No significant changes were observed in NPY., Conclusions: We report an increase in prevalence of ocular discomfort in patients with GERD/LPR. The observations of VIP and NPY transcripts demonstrate the potential neurogenic nature of the inflammatory state. Restoration of the ocular surface parameters suggests the potential usefulness of topical alginate therapy., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: To report three cases of massive pseudophakic macular edema occurring the day after uneventful cataract surgery and resolving in 24 to 72 hours., Methods: Observational case series., Results: A 68-year-old woman affected by systemic lupus erythematosus and antiphospholipid syndrome displayed massive macular edema on optical coherence tomography scan one day after uneventful cataract surgery. Routine postoperative topical eye drops (chloramphenicol/betamethasone 4 times a day and bromfenac 2 times a day) were continued without additional medications. Three days later, optical coherence tomography showed a completely recovered, normal fovea. Two similar cases were documented. A 73-year-old man and a 53-year-old man underwent cataract surgery and started the mentioned topical postoperative therapy. Severe macular edema was diagnosed the day after surgery and resolved in 24 and 48 hours, respectively., Conclusion: Massive macular edema may occur immediately after uncomplicated cataract and then disappear within 1 to 3 days, without invasive therapies. This is a very significant event that may follow cataract surgery, and that was previously unreported.

Purpose: Ocular mucous membrane pemphigoid (OcMMP) is a rare eye disease characterized by relapsing-remitting or persisting long-lasting inflammatory events associated with progressive scarring. Despite long-term immunomodulating therapy, abnormal fibrosis keeps worsening in patients with OcMMP. This study investigates the fibrotic process in patients with OcMMP, as well as the critical role of the epithelium in modulating the local fibrosis., Methods: In this prospective, observational pilot study, patients affected by long-lasting OcMMP were compared with age- and gender-matched healthy controls. Clinical grading was assessed, and conjunctival biopsy and impression cytology were performed. Conjunctival samples were used for quantifying the expression of transcripts regulating the inflammatory and fibrogenic processes., Results: Ocular surface clinical and functional markers worsened in patients with OcMMP with fibrotic disease progression. In more advanced disease stages, both impression cytologies and conjunctival biopsies revealed increased tissue remodeling and profibrotic markers (α-SMA and TGF-β), and decreased levels of inflammatory markers (I-CAM1, IL-10, and IL-17). Increased epithelial expression of profibrotic markers and histological changes were detected., Conclusions: Chronic OcMMP is characterized by a progressive, aberrant self-sustaining fibrotic process that worsens clinical signs and symptoms. Conjunctival epithelial cells may transdifferentiate into myofibroblast-like phenotypes when chronically exposed to high levels of inflammation, as in the case of OcMMP. Tissue remodeling markers in OcMMP could be used as early diagnostic, prognostic, and therapeutic biomarkers, harvested in a non-invasive and painless procedure such as impression cytologies.

Introduction: Inverted Internal Limiting Membrane (ILM)-flap technique demonstrated its effectiveness, in terms of anatomical closure rate and visual acuity recovery for high myopic macular holes. We evaluated macular function after a successful inverted ILM-flap for macular holes in high myopic eyes (hMMH) using microperimetry to predict visual prognosis., Methods: A retrospective study on 23 eyes of 23 patients after surgical closure of hMMH, was performed. All patients underwent inverted ILM-flap and gas tamponade. Cataract surgery was performed in phakic eyes. Study outcomes including best-corrected visual acuity (BCVA), retinal sensitivity (RS) at central 12°, central retinal sensitivity (CRS) at central 4° and mean deviation (MD), and fixation behavior as bivariate contour ellipse area (BCEA, degrees2) measured by microperimetry, were evaluated over 6 months. A mixed-effects model was used to evaluate and compare the repeated measurements of outcomes between phakic and pseudophakic eyes. A regression model was performed to assess the relationship between BCVA at 6 months and independent variables., Results: Overall mean BCVA improved from 0.98 ± 0.21 logMAR at baseline to 0.47 ± 0.31 logMAR at the last follow-up ( p  < 0.001). Over 6 months, overall sensitivity measurements improved (RS, p  = 0.001; CRS, p  < 0.0001; MD, p  = 0.03), and the BCEA decreased in dimension, although not significantly ( p  ≥ 0.05). The mixed model revealed a significantly better effect of inverted ILM-flap combined with cataract surgery on BCVA and CRS in phakic eyes than inverted ILM-flap alone in pseudophakic ones. The regression model revealed a relationship of 6-month BCVA with pre-operative BCVA ( β  = 0.60, p  = 0.02) and RS ( β  = -0.03, p  = 0.01)., Conclusion: The inverted ILM-flap technique significantly improved visual acuity and retinal sensitivity after the hMMH closure, particularly when combined with cataract extraction. Pre-operative visual acuity and retinal sensitivity at central 12° may predict post-surgical visual acuity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sborgia, Boscia, Niro, Landini, Pastore, Albano, Piepoli, Donghia, Dore, Viggiano, Buonamassa, Di Pardo, Molfetta, Eye Clinic Research Group, Coassin, Dell’Omo, Boscia, Alessio and Sborgia.)

Dry Eye Disease (DED) is an increasingly common condition that affects between 5% and 50% of the global population. Even though DED is most frequently diagnosed in older people, it has also been diagnosed in young adults and adolescents more frequently in recent years (employees, gamers). People can experience different types of symptoms and find it challenging to read, watch TV, cook, climb stairs, and meet friends. Mild and severe dry eye can reduce quality of life similarly to mild psoriasis and moderate-to-severe angina. Furthermore, DED patients experience serious difficulties driving vehicles, especially at night, and show a decrease in work productivity, which, when combined with the relevant indirect cost that this condition produces, poses a serious challenge in our days. In addition, DED patients are more likely to develop depression and suicidal ideations and experience frequent sleep disorders. Finally, it is discussed how lifestyle changes, such as increased physical activity, blinking exercises, and a proper diet, have positive implications for the management of this condition. Our aim is to draw attention to the negative effects of dry eye in real life, which are unique to each patient, especially as they relate to the non-visual symptoms experienced by DED patients.

Background: Microperimetric biofeedback training improved visual acuity and fixation stability in patients who previously underwent macular surgery. We aimed to compare the functional results of biofeedback training with the standard of care in patients who underwent successful inverted Internal Limiting Membrane (ILM)-flap technique for high myopic macular holes (hMMH)., Methods: This was a retrospective, comparative, cohort study. Patients with hMMH after surgical hole closure underwent microperimetric biofeedback using structured light stimulus plus acoustic tone (n = 12; Biofeedback) or standard of care with scheduled visits (n = 11; Control). Best-corrected visual acuity, retinal sensitivity at central 12° (RS) and 4° (CRS) with a mean deviation at central 12° (MD), and fixation stability as bivariate contour ellipse area (BCEA 68%, 95%, and 99%) were assessed at baseline and month 1, 3, 6, and 12. The Mann-Whitney test was used to test the difference between the groups., Results: Baseline functional parameters were not significantly different among the groups. BCVA significantly improved in each group (Biofeedback, p = 0.002; Control, p ≤ 0.02) at all follow-up visits. CRS significantly improved at 6 ( p = 0.03) and 12 ( p = 0.01) months in the Biofeedback group and at month 12 ( p = 0.01) in the Control group. RS ( p = 0.001) and MD ( p = 0.005) improved at the last follow-up only in the trained group. After training, BCEA 68% and 95% significantly improved (6 and 12 months, p < 0.05). The Biofeedback group had better results in RS ( p ≤ 0.02), CRS ( p ≤ 0.02), and BCEA 68%, 95%, and 99% ( p ≤ 0.01) compared to the Control at all follow-ups. BCVA and MD were better in the Biofeedback group at month 3 ( p = 0.01), and month 3 ( p = 0.01) and 12 ( p = 0.003), respectively., Conclusions: Microperimetric biofeedback can increase retinal sensitivity and stabilize fixation better than the standard care over months after a successful inverted ILM-flap for hMMH.

Purpose: Laryngopharyngeal reflux (LPR) is a common worldwide disease. LPR symptoms may involve distant organs and tissues including the ocular surface with manifestations of a Dry Eye-like disease. We evaluated the concomitant involvement of the ocular surface in patients with LPR. We also defined the clinical signs and the roles of chemical and neuro-inflammatory mediators in the tears of LPR patients., Methods: Seventy-seven patients with LPR (mean age 65.8 ± 16.8 SD) and 25 healthy controls (mean age 56.5 ± 16.3 SD) were recruited from the otorhinolaryngology unit. Each subject was evaluated for the presence of concomitant ocular surface disease through clinical examination, including the measurement of tear break-up time (TBUT) and the Ocular Surface Disease Index (OSDI) questionnaire. Tears and conjunctival imprints were collected. The presence of pepsin in tears was detected by ELISA. HLA-DR in conjunctival imprints were imaged by immunofluorescence microscopy. RT-PCR quantified conjunctival mRNA transcripts of HLA-DR, IL-8, MUC5AC, NADPH, VIP, and NPY., Results: Patients with LPR had significantly increased OSDI and reduced TBUT scores compared to control subjects ( p  < 0.05 each). Pepsin was detected in 51% of patient tears while it was not measurable in the controls ( p  < 0.01). Immunoreactivity for HLA-DR in the conjunctival impressions was greater than for the controls with an increased mRNA expression ( p  < 0.05). mRNA transcripts for IL-8, NADPH, and VIP were significantly increased in LPR patients ( p  < 0.05 each), but neither MUC5AC nor NPY was different from controls., Conclusions: LPR can adversely affect the ocular surface, leading to moderate signs and symptoms of dry eye. This study provides evidence that the presence of pepsin, HLA-DR immunoreactivity, and increased mRNA expression of neuro-inflammatory markers in the tears and conjunctival imprints of LPR patients suggests a potential link between LPR inflammation and ocular surface disease.

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye.In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients.In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients' symptoms that could manifest in the postoperative time.

Background: Dry eye disease (DED) is a common and debilitating condition that affects millions of people worldwide. Despite its prevalence, the diagnosis and management of DED can be challenging, as the condition is multifactorial and symptoms can be nonspecific. In recent years, there have been significant advancements in diagnostic technology for DED, including the development of several new devices., Methods: A literature review of articles on the dry eye syndrome and innovative diagnostic devices was carried out to provide an overview of some of the current high-tech diagnostic tools for DED, specifically focusing on the TearLab Osmolarity System, DEvice Hygrometer, IDRA, Tearcheck, Keratograph 5M, Cornea Dome Lens Imaging System, I-PEN Osmolarity System, LipiView II interferometer, LacryDiag Ocular Surface Analyzer, Tearscope-Plus, and Cobra HD Camera., Conclusions: Despite the fact that consistent use of these tools in clinical settings could facilitate diagnosis, no diagnostic device can replace the TFOS algorithm.

Our aim is to describe local tissue remodeling in a cohort of adult VKC patients. Male patients diagnosed with active VKC were enrolled in an open pilot study into two groups according disease onset: childhood classic VKC and adult VKC. Visual acuity and ocular surface clinical examination focusing on chronic inflammatory sequelae and impression cytology were performed in all enrolled subjects. Conjunctival imprints were processed for molecular, biochemical and immunofluorescent analysis for tissue remodeling (TGFβ1,2,3 and αSMA) and epigenetic (DNMT3a, Keap1; Nrf2) markers as well as androgen receptors were investigated and compared between groups. Clinical assessment showed increased conjunctival scarring in adult VKC compared to classic VKC. Immunoreactivity for αSMA and expression of TGFβ were higher in adult VKC group. Significantly higher levels of TGFβ3 (3.44 ± 1.66; p < 0.05) were detected in adult VKC compared to childhood VKC, associated with an increasing trend of TGFβ1 (1.58 ± 0.25) and TGFβ2 (1.65 ± 0.20) isoforms levels. Molecular analysis showed a relative increase in tissue remodeling/fibrogenic transcripts (TGFβ isoforms and αSMA) associated to a significant increase of selective epigenetic targets (DNMT3, Nrf2 and keap1) in adult VKC phenotype. Increased local conjunctival androgen receptors was detected in patients with adult variants compared to classic childhood VKC and healthy subjects. Finally, a direct correlation between TGFβ and androgen receptor expression was also detected. A pro-fibrotic clinical and biomolecular trait was unveiled in adult variant of VKC, which causes ocular surface disease and visual impairment., (Copyright © 2022. Published by Elsevier Ltd.)

Purpose: To develop and perform ex vivo testing for a device designed for semiquantitative determination of intracorneal dissection depth during big bubble (BB) deep anterior lamellar keratoplasty., Methods: A prototype device connected to a syringe and cannula was designed to determine depth of intrastromal placement based on air rebound pressure emitted by a software controlled generator. Ex vivo testing of the device was conducted on human corneas mounted on an artificial anterior chamber in three experiments: (1) cannula purposely introduced at different depths measured with anterior segment optical coherence tomography, (2) cannula introduced as per the BB technique, and (3) simulation of the BB technique guided by the device., Results: A positive pressure differential and successful BB were observed only when the cannula was positioned within 150 microns from the endothelial plane. In all successful BB cases (21/40), a repeatable increase in tissue rebound pressure was detected, which was not recorded in unsuccessful cases. The device was able to signal to the surgeon correct placement of the cannula (successful BB) in 16 of 17 cases and incorrect placement of the cannula (unsuccessful BB) in 8 of 8 cases (94.1% sensitivity, 100% specificity)., Conclusions: In our ex vivo model, this novel medical device could reliably signal cannula positioning in the deep stroma for effective pneumatic dissection and possibly aid technical execution of BB deep anterior lamellar keratoplasty., Translational Relevance: A medical device that standardizes big bubble deep anterior lamellar keratoplasty could increase the overall success rate of the surgical procedure and aid popularization of deep anterior lamellar keratoplasty.

Purpose: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL)., Methods: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group., Results: Forty-three eyes of 22 subjects with histology-proven VRL were included. Mean time of survival was 64.8 months (SE±10.8). Twelve patients (57%) presented CNS involvement, which was significantly associated with progression (r = 0.48, P = .03) and death (r = 0.56, P = .009). The isolated primary VRL group had a 5-year OS of 80%. Combined systemic and local chemotherapy reduced the risk of death by 82% (hazard ratio 0.18[0.04- 0.85]) in the entire cohort., Conclusion: Combined systemic and local chemotherapy significantly improved OS but not PFS of patients affected by VRL.

Purpose: To evaluate overall patient satisfaction, spectacle independence, visual acuity, and prevalence of optical phenomena following bilateral implantation of a new non-diffractive extended depth-of-focus intraocular lens targeted for minimonovision., Methods: Multicenter prospective case series. Postoperative far and near visual acuity at 3 months and patient quality of life by NEI-VFQ-25 questionnaire were assessed. Postoperative evaluation included defocus curves analysis, spectacle independence assessment, and recording of photic phenomena., Results: The study enrolled 97 eyes of 59 patients that underwent femtosecond-assisted cataract surgery with AcrySof IQ Vivity intraocular lens implantation. Thirty subjects (60 eyes) were eligible for analysis. After 3 months, postoperative achieved binocular uncorrected visual acuity was -0.03  ±  0.06 logarithm of the minimum angle of resolution for distance, 0.06  ±  0.06 logarithm of the minimum angle of resolution for intermediate, and 0.19  ±  0.03 logarithm of the minimum angle of resolution for near. Defocus curve showed a smooth profile with no abrupt decrease of visual acuity. Minimonovision significantly improved visual acuity compared to when minimonovision was neutralized, for values of defocus curves from -1 to -3 D ( p  < 0.05). Twenty-six (87%) patients reported complete spectacle independence. High levels of satisfaction for distance and near vision resulted at VFQ-25 questionnaire. Only two patients complained of halos (6.7%) and one of them also of glare (3.3%)., Conclusions: Implantation of this new non-diffractive extended depth-of-focus intraocular lens with minimonovision resulted in satisfying far, intermediate, and near visual acuity with a consistent reduction of spectacle dependence and improvement in patient's quality of life.

Purpose: To evaluate the mid-term safety and effectiveness of intravitreal dexamethasone implant (DEX-i) for treating unresponsive to medical therapy cystoid macular edema (CME) in vitrectomized eyes for endophthalmitis., Methods: Retrospective and interventional case series study conducted on vitrectomized eyes for endophthalmitis that developed a CME that did not adequately respond to medical therapy, who underwent 0.7-mg DEX-i. Main outcome measures were changes in central retinal thickness (CRT) and best corrected visual acuity (BCVA)., Results: Eleven eyes were included in the study. Microbiological findings of vitreous biopsies were 7 (63.6%) staphylococcus epidermidis; 3 (27.3%) Pseudomonas aeruginosa; and 1 (9.1%) Propionibacterium acnes. Median (interquartile range, IqR) duration of CME was 4.0 (3.0-4.0) months. Median (IqR) time between vitrectomy and DEX-i was 9.0 (9.0-11.0) months. Median CRT was significantly decreased from 548.0 (412.8-572.5) µm at baseline to 308.0 (281.3-365.5) µm at month 6 (p = 0.0009, Friedman test). Median BCVA significantly improved from 38.0 (30.5-44.8) letters at baseline to 50.0 (46.8-53.0) letters at month 6 (p < 0.0001, Friedman), with 9 (81.8%) eyes gaining ≥ 10 letters. Elevation of intraocular pressure was observed in one (9.1%) eye, which was successfully controlled with medical therapy. No recurrence of endophthalmitis or other complications was observed. Eight (72.7%) eyes required an additional DEX-i, while 3 (27.3%) were successfully controlled with only one DEX-i. CME recurrence occurred in 5 (62.5%) Gram-positive and 3 (100.0%) Gram-negative bacteria (p = 0.2357)., Conclusion: In vitrectomized eyes for endophthalmitis affected by CME unresponsive to medical therapy, DEX-i had an acceptable safety profile and achieved favorable outcomes. The possibility of suppressing mechanisms for infection control should be taken into account, although correct management of endophthalmitis and long time without reactivation before DEX-i reduce the risk., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To evaluate the efficacy of Rituximab (RTX) therapy in patients affected by Vogt-Koyanagi-Harada (VKH) disease poorly controlled by traditional immunosuppressive treatment., Methods: Retrospective case series of recurrent VKH uveitis treated with intravenous RTX between January 2019 and November 2020. All patients were treated with intravenous RTX and underwent complete ophthalmic examination, best-corrected visual acuity (BCVA), fundus photography, subfoveal choroidal thickness (SFCT) measurement on enhanced depth imaging optical-coherence tomography (EDI-OCT), fluorescein, and indocyanine green angiography., Results: Five patients were included. All patients received at least 3 RTX infusions. Mean BCVA improved from 20/32 Snellen equivalent at baseline before RTX treatment to 20/28 Snellen equivalent ( p = .008). Mean SFCT on EDI-OCT showed a reduction from 564.4 µm(SD = 176.2) to 280.0 µm(SD = 140.4) ( p = .015). Follow-up ranged from 12 to 21 months, with a mean of 18.2 ± 3.7 months., Conclusions: In these case series, RTX was effective in VHK disease poorly controlled by traditional immunosuppressive treatment.

Ageing has been defined as a specific individual plasticity and remodeling capacity to the environment' insults and stimuli. The precise physiology of aging is not entirely understood. Several theories have been proposed and included programmed cell death, genetic mutations, the epigenetic clock, wear-and-tear and free radicals. Ocular surface represents a complex morpho-functional unit composed of different tissues that strictly interact to preserve homeostasis and function. Ageing severely disrupts this system by means of inflammaging and immunosenescence, leading to ocular surface failure in older population., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: To evaluate changes in Toll Like Receptors (TLRs) expression at the ocular surface of healthy volunteers within different age groups., Methods: Fifty-one healthy volunteers were enrolled in a pilot observational study. Clinical function tests (OSDI questionnaire, Schirmer test type I and Break Up time) were assessed in all subjects. Temporal Conjunctival imprints were performed for molecular and immunohistochemical analysis to measure TLRs expression (TLR2, 4, 3, 5, 7, 8, 9 and MyD88)., Results: Immunofluorescence data showed an increased TLR2 and decreased TLR7 and TLR8 immunoreactivity in old conjunctival imprints. Up-regulation of TLR2 and down-regulation of TLR7, TLR8 and MyD88 transcripts expression corroborated the data. A direct correlation was showed between increasing ICAM-1 and increasing TLR2 changes with age. Within the age OSDI score increases, T-BUT values decrease, and goblet cells showed a decreasing trend., Conclusion: Changes in TLRs expression are associated with ageing, suggesting physiological role of TLRs in modulating ocular surface immunity. TLRs age related changes may participate to the changes of ocular surface homeostatic mechanisms which lead to inflammAging., (© 2022. The Author(s).)

Purpose: The purpose of this article was to compare clinical outcomes between therapeutic penetrating keratoplasty (TPK), therapeutic deep anterior lamellar keratoplasty (TDALK), and optical penetrating keratoplasty (OPK) in Acanthamoeba keratitis., Methods: A literature search was conducted in online libraries from 1980 to 2021. The primary end points were best-corrected visual acuity (VA), graft survival, and infection recurrence. In addition, we enrolled 35 consecutive patients with AK from our practice evaluating best-corrected VA and high-order aberrations., Results: A total of 359 AK eyes from 33 published studies were retrieved from 175 publications screened. One hundred sixty-five eyes (73%) that underwent TPK and 39 eyes (84%) treated with TDALK had a clear graft at the last follow-up visit. Only the patients treated with OPK had 82 clear grafts (94%) during the follow-up period. Forty-seven (21%) of TPK patients reached VA ≥20/30, compared with 11 (25%) of TDALK patients and 35 (40%) of OPK patients. Acanthamoeba infection recurrence occurred in 38 eyes (16.8%) that underwent TPK, 9 (19%) that underwent TDALK, and 8 (9.5%) that underwent OPK. In our series, best-corrected visual acuity in nonsurgically treated patients was 1 ± 0.50 logMAR compared with 0 logMAR of surgically treated patients. High-order aberrations were significantly lower in surgically treated eyes after AK resolution, particularly in TDALK when compared with TPK patients. Best-corrected visual acuity was better in TDALK patients compared with TPK patients., Conclusions: After AK resolution by 6 to 12 months of medical treatment, OPK seems to be the best surgical choice in patients with AK. If AK could not be eradicated by medical therapy, TDALK may be chosen in the early disease stage and TPK in later stages., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Epstein-Barr Virus (EBV) has been previously reported to cause rare occurrence of mostly epithelial and nummular keratitis. We hereby report two patients developing bilateral peripheral deep interstitial keratitis following EBV-related infectious mononucleosis (IM)., Description of Cases: Two female adolescents presented with findings of chronic relapsing posterior interstitial keratitis with neovascularisation mostly located in the superior and inferior peripheral cornea, in absence of signs of anterior uveitis. The disease presented months after the occurrence of IM. Other etiologies of interstitial keratitis were excluded. EBV DNA could not be detected in the aqueous humor of both patients. The patients responded promptly to topical corticosteroids, with multiple recurrences reported in one case., Conclusion: EBV-induced IM can cause bilateral peripheral interstitial keratitis with delayed onset. Progressive relapsing course of the keratitis can be observed.

Background: To report the long-term effects of the new rhNGF treatment on corneal sensitivity in patients with., Cases Presentation: We present three cases of corneal ulcers due to NK that were treated with rhNGF. In each patient wound healing evolution was documented by clinical pictures and corneal sensitivity measured by Cochet-Bonnet aesthesiometry. Best corrected visual acuity and Type I Schirmer test were also assessed neurotrophic keratopathy.All patients healed within 8 weeks and NK showed no recurrences in the mean follow-up period of 35 weeks. Each subject showed a significant increase of corneal sensitivity and tear secretion, with concomitant improvement in visual acuity., Conclusion: Corneal sensitivity, measured by Cochet-Bonnet aesthesiometer, markedly increased in all eyes. Further studies are warranted to demonstrate a possible mechanism of nerve restoration with rhNGF treatment.

Purpose: To evaluate postoperative safety of femtosecond laser deep anterior lamellar keratoplasty performed with an innovative anvil profile in keratoconus patients., Methods: This is a single-center, retrospective cohort study. We reviewed medical records of 89 keratoconus patients that underwent femtosecond laser deep anterior lamellar keratoplasty surgery (46 eyes) and manual deep anterior lamellar keratoplasty (47 eyes). Inclusion criteria required: age > 18 years old, best-corrected visual acuity < 0.3 LogMAR, continuous suture of the graft, postoperative immunomodulant regimen with dexamethasone 0.1% for 6 months and at least 12 months follow-up. Previous eye surgery, hydrops, and other ocular disease were excluded. The main outcome measures were postoperative events: rejections, persistent epithelial defects, and graft failures., Results: During the follow-up (20 ± 6 months) graft rejection was diagnosed in 0 of femtosecond laser deep anterior lamellar keratoplasty versus 6 (17%) of manual deep anterior lamellar keratoplasty [ p 0.027], persistent epithelial defect in 0 of femtosecond laser deep anterior lamellar keratoplasty versus in 4 (11%) of manual deep anterior lamellar keratoplasty [ p 0.048] and graft failure occurred in 4 (11%) of manual deep anterior lamellar keratoplasty. The best-corrected visual acuity, after removal of sutures, was better in the femtosecond laser deep anterior lamellar keratoplasty group 0.09 ± 0.08 LogMAR versus 0.16 ± 0.13 LogMAR in manual deep anterior lamellar keratoplasty [ p 0.035] group although refractive spherical equivalent and cylinder, topographic average keratometry and cylinder were similar., Conclusions: Anvil-shaped femtosecond laser deep anterior lamellar keratoplasty in keratoconus surgery increases safety and readiness of recovery, decreasing the incidence of corneal rejection, epithelial defects, graft failures, and producing better best-corrected visual acuity after removal of sutures.

Objectives: To analyze the effect of the employment of polyvinylpyrrolidone-iodine (PVP-I) 0.6% eye drop on the clinical course of patients affected by Adenoviral Keratoconjunctivitis (AKC)., Methods: Consecutive patients with clinical signs of AKC and positive results of AdenoPlus test were enrolled from four Italian Centres. Patients were randomized to receive: PVP-I 0.6% eye drops four times/daily for 20 days (Group A) or hyaluronate-based tear substitutes four times/daily for 20 days (Group B). Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) Optovue iVue pachymetry map; corneal haze; conjunctival injection and chemosis; subepithelial corneal infiltrates (SEIs); corneal and conjunctival staining and corneal densitometry were recorded at diagnosis and at every follow-up visit. The primary outcome was the resolution time of AKC., Results: Overall, 59 AKC patients (34 for Group A and 25 for Group B) completed the study. Patients of Group A showed a significantly shorter resolution time and lower incidence of SEIs compared to patients of Group B. In particular, SEIs were present at the last visit in 3/34 (8.82%) patients of the Group A vs 11/25 (44%) of the Group B (p = 0.005). Patients of Group A showed a significantly lower incidence of corneal haze compared to patients of Group B (0/34 vs 3/25; p = 0.038). No side effects were reported for both groups., Conclusions: Although further clinical evaluations are needed, according to our data the use of PVP-I 0.6% eye drop in the setting of AKC reduces the risk of SEIs as well as the resolution time of the disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.)

Corneal transplantation is one of the most successful forms of solid organ transplantation; however, immune rejection is still a major cause of corneal graft failure. Both innate and adaptive immunity play a significant role in allograft tolerance. Therefore, immune cells, cytokines, and signal-transduction pathways are critical therapeutic targets. In this analysis, we aimed to review the current literature on various immunotherapeutic approaches for corneal-allograft rejection using the PubMed, EMBASE, Web of Science, Cochrane, and China National Knowledge Infrastructure. Retrievable data for meta-analysis were screened and assessed. The review, which evaluated multiple immunotherapeutic approaches to prevent corneal allograft rejection, showed extensive involvement of innate and adaptive immunity components. Understanding the contribution of this immune diversity to the ocular surface is critical for ensuring corneal allograft survival.

A foldable acrylic intraocular lens (IOL) with a 6.0 mm optic was removed through a 2.2 mm corneal incision as a single piece with minimal wound trauma. By viscodissection, the IOL was freed from its position in the capsular bag and moved into the anterior chamber. Vannas scissors were introduced through a 2.2 mm corneal incision. A 4.5 mm straight slit was cut at each optic-haptic junction on opposite sides, perpendicular to each haptic shaft. This pair of parallel cuts generated 3 IOL segments in an S configuration that remained connected. The IOL was grasped by 1 haptic and removed as a single piece., (Copyright © 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS.)

Objective: Mechanisms of action and optimal stimulation parameters of transcutaneous auricular vagus nerve stimulation (taVNS) are currently unknown. Pupil size has gained attention as a promising biomarker of vagal activation in different studies on animal models. The aim of this study is to investigate the effects of taVNS on pupil diameter in healthy subjects., Methods: All subjects received taVNS at the left external acoustic meatus and control stimulation at the left earlobe during the same experimental session. Different intensities (0.5 mA; 1.0 mA; 2.0 mA; 3.0 mA) for both conditions were tested. Tonic pupil size was recorded in both eyes at baseline and during each stimulation using an infrared-automated pupillometer in three different illuminance conditions (scotopic, mesopic, photopic)., Results: In scotopic illuminance condition, a significant interaction between intensity and condition (real vs control) was found for the left eye. Post-Hoc analysis showed that during real taVNS at 2 mA, pupil size was significantly larger in comparison to baseline and 2 mA control stimulation., Conclusions: Our study demonstrates that taVNS induces pupil dilation under specific illuminance conditions and at specific stimulation intensity., Significance: The effects of taVNS are strictly dependent on technical aspects, such as stimulation parameters and experimental set-up., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Nowadays, the continuous increase in air pollution has significantly changed air quality, leading to the onset of the so-called urban syndrome (US), an allergic-like conjunctivitis triggered by pollutants. These patients are characterized by persistent dysregulation of ocular surface para-inflammation, causing chronic low-grade inflammation and ocular discomfort, with significant consequences for occupational health and job productivity prospects. This study aims to investigate the effects of topical glycerophosphoinositol (GPI) eye drops on the signs and symptoms of US., Methods: A multicenter prospective open interventional study was performed. Patients affected by US, enrolled from occupational medicine clinics, were treated with eye drops containing 0.001% GPI in 0.2% HA vehicle three times a day. Ocular surface disease index (OSDI), tear break-up time (T-BUT), Schirmer test, Oxford score, hyperemia and ocular surface symptoms were recorded at patient enrolment (T0), after 1 week (T1) and after 1 month (T2) of treatment., Results: A total of 113 consecutive patients (226 eyes) were included. OSDI score displayed a significant improvement after one week (T0: 39.9 ± 19, T1: 20.8 ± 17.9, T2: 18.4 ± 15.6, p < 0.0001); T-BUT (T0: 5.2 ± 2, T1: 7.7 ± 2.2, T2: 9.7 ± 1.8, p < 0.0001) and Schirmer Test (T0: 6.6 ± 2.4, T1: 9.7 ± 2.7, T2: 12.6 ± 2.6, p < 0.0001) progressively improved from T0 to T2., Conclusions: trice-daily topic instillation of 0.001% GPI in 0.02% HA vehicle resulted an effective and well tolerated treatment in US patients.

Topic : To focus on endogenous endophthalmitis management, particularly etiology-based medical and surgical therapy. Methods : Literature search of published studies from July 1990 to February 2019 on endogenous endophthalmitis available on PubMed was made without any language constraints. Results : A total of 78 articles were retrieved from 728 initially analyzed and 62 studies were included. Although the superiority of vitrectomy over tap and inject techniques is controversial, the most recent publications favor an early surgical approach for endogenous endophthalmitis. Vitrectomy is useful in severe cases complicated by marked vitreous opacity, retinal detachment, poor initial visual acuity, and more virulent pathogens. Oral or intravenous antibiotics are also necessary to treat systemic infection. Vitrectomy is superior to blood cultures in diagnosing the etiology of infection. Conclusions : Endogenous endophthalmitis is an important cause of visual acuity impairment. Prompt treatment with appropriate use of pharmacological or surgical therapy is mandatory to preserve visual function. Abbreviations : IOP: intra-ocular pressure; AIDS: acquired immune deficiency syndrome; EVS: endophthalmitis vitrectomy study; CEVE: complete and early vitrectomy for endophthalmitis.

Background: Dry eye syndrome (DES) is strictly connected to systemic and topical sex hormones. Breast cancer treatment, the subsequent hormonal therapy, the subsequent hyperandrogenism and the early sudden menopause, may be responsible for ocular surface system failure and its clinical manifestation as dry eye disease. This local dryness is part of the breast cancer iatrogenic dryness, which affects overall mucosal tissue in the fragile population of those with breast cancer., Methods: A literature review regarding the role of sex hormone changes and systemic hormonal replacement treatments (SHRT) in DES available on PubMed and Web of Science was made without any restriction of language., Results: Androgens exert their role on the ocular surface supporting meibomian gland function and exerting a pro-sebaceous effect. Estrogen seems to show a pro/inflammatory role on the ocular surface, while SHRT effects on dry eye are still not well defined, determining apparently contradictory consequences on the ocular surface homeostasis. The role of sex hormones on dry eye pathogenesis is most likely the result of a strict crosstalk between the protective androgens effects and the androgen-modulating effects of estrogens on the meibomian glands., Conclusions: Patients with a pathological or iatrogenic hormonal imbalance, such as in the case of breast cancer, should be assessed for dry eye disease, as well as systemic dryness, in order to restore their social and personal quality of life.

Purpose : To unveil the long-term prognosis of Acanthamoeba keratitis based on clinical presentation and timing of diagnosis to better inform patients since the first visit regarding their length of treatment, quality of life, and visual function. Methods : Retrospective observational study enrolling patients with Acanthamoeba keratitis from 1994 to 2019. Patients with a complete eye examination and medical records were analyzed. The severity of the disease, the time from onset of symptoms to the appropriate therapeutic regimen, the time until clinical resolution, visual function, and long term follow-up was evaluated. Quality of life was assessed at the last follow-up visit by means of the VFQ-25 questionnaire. Results : Thirty-five patients (40 eyes) were assessed. The overall healing time of patients with Acanthamoeba keratitis was 12.5 ± 3.5 months, while patients with a severe corneal ulcer (stage III) had a significant longer healing time (16.2 ± 3.7 months) compared to patients with stage II (7.04 ± 0.7 months) or I (7.7 ± 1.5 months; p < .05). Patients who received a prompt therapy (<30 days form symptoms onset) had a reduced healing time compared to patients with a delayed diagnosis ( p < .01). Quality of life was assessed after a mean of 11.7 ± 4.7 years and it was mildly reduced (86.6 ± 17). Patients that were diagnosed early (<30 days from onset) showed a lower reduction in quality of life than in patients that were diagnosed >30 days from onset. After resolution, 59% of the patients considered unnecessary any further proposed surgical intervention. Conclusions : Delayed diagnosis of Acanthamoeba keratitis and disease severity significantly increases healing time and duration of treatment. The time to diagnosis and disease stage at diagnosis predicts the duration of treatment, the final outcome, quality of life, and the requirement of surgery. These data would allow us to promptly inform patients about long-term disease timeline, future outcomes, improving disease acceptance, and quality of life.

Purpose: To review the current adoption of laser flare and cell photometry (LFCP) in the setting of modern cataract surgery to analyze inflammation aiming to identify evidence of a correlation between LFCP values and the risk of cystoid macular edema (CME) development., Methods: An extensive PubMed literature search was performed to review all the published studies investigating inflammation by LFCP after uncomplicated phacoemulsification. The following keywords were used: cataract surgery, cystoid macular edema, anterior chamber inflammation, laser flare, and cell photometry., Results: Seventy-eight original articles investigating inflammation by LFCP were selected. Macula alterations were searched in 12 (15%) trials, by optical coherence tomography or fluorescein angiography in 11 (14%) and 1 (1%) studies, respectively. Among them, 9 (12%) papers investigated the correlation between LFCP values and cystic changes to the macula: 7 (9%) and 2 (3%) studies identified a positive and negative correlation, respectively. Three (4%) papers did not perform any correlation analysis., Conclusion: CME, as a consequence of uncontrolled postoperative inflammation, is a common cause for unfavorable visual outcomes following uncomplicated phacoemulsification with IOL implantation. After surgery, intraocular inflammation is generally assessed by qualitative methods. Although well-established and practical in uveitis, they are inadequate to detect the modest inflammatory response that usually occurs after uneventful phacoemulsification. LFCP correlate with the chance of macula alteration after surgery and higher the values higher the risk of CME. The quantitative analysis of intraocular inflammation by LFCP after cataract surgery might be a tool to predict the risk of pseudophakic CME.

This study compared the outcomes of cataract surgery with intraocular lens (IOL) implantation in patients with juvenile idiopathic arthritis (JIA)-associated chronic anterior uveitis treated with antimetabolite drugs and systemic corticosteroids (Non-Biological Group) versus patients treated with antimetabolites and biological drugs (Biological Group). A cohort of patients with cataract in JIA-associated uveitis undergoing phacoemulsification with IOL implantation was retrospectively evaluated. The main outcome was a change in corrected distance visual acuity (CDVA) in the two groups. Ocular and systemic complications were also recorded. The data were collected preoperatively and at 1, 12, and 48 months after surgery. Thirty-two eyes of 24 children were included: 10 eyes in the Non-Biological Group and 22 eyes in the Biological Group. The mean CDVA improved from 1.19 ± 0.72 logMAR preoperatively to 0.98 ± 0.97 logMAR at 48 months ( p = 0.45) in the Non-Biological Group and from 1.55 ± 0.91 logMAR preoperatively to 0.57 ± 0.83 logMAR at 48 months ( p = 0.001) in the Biological Group. The postoperative complications, including synechiae, cyclitic membrane, IOL explantation, glaucoma, and macular edema, were not statistically different between the two groups. An immunosuppressive treatment with biological drugs can improve the visual outcome after cataract surgery in patients with JIA-associated uveitis, but it does not significantly reduce postoperative ocular complications.

Purpose: Previous reports described unfavorable visual outcomes after surgery for uveitic macular pucker. Our goal was to demonstrate that patients with history of uveitis may benefit from vitrectomy for epiretinal membrane if executed under appropriate circumstances., Methods: We performed pars plana vitrectomy with ERM and ILM peeling in patients with post-uveitic macular pucker who did not show signs of ocular inflammation for at least 3 months after the suspension of immunosuppressive therapy. Visual acuity, central macular thickness at OCT, ocular inflammation, and complications were recorded., Results: Twenty-six eyes were operated. Mean duration of follow-up was 67 months. Visual acuity significantly improved from 20/80 to 20/40 after surgery. Vision increased in 20 (77%), remained stable in 4 (15%), and decreased in 2 (8%) eyes. Best-corrected visual acuity ameliorated by at least 2 ETDRS lines in 14 eyes (54%). Contingency analysis did not show any statistical difference among the different types of uveitis ( p  = 0.46). Mean central foveal thickness improved postoperatively (428 ± 104 vs 328 ± 130 microns; p  = 0.017)., Conclusion: Patients with uveitic epiretinal membrane benefit from vitrectomy with membranectomy if operated when intraocular inflammation had subsided.

Background/purpose: Full-thickness macular hole is a complication of idiopathic macular telangiectasia type 2 with a low surgical closure rate and a poor functional recovery. We analyze morphologic and functional outcomes after an inverted internal limiting membrane-flap technique for full-thickness macular hole complicating idiopathic macular telangiectasia type 2 using optical coherence tomography and microperimetry., Case Report: A 77-year-old man presented us complaining visual impairment in the left eye (20/40) due to a full-thickness macular hole complicating idiopathic macular telangiectasia type 2. The patient underwent vitrectomy with an inverted internal limiting membrane-flap technique and injection of 22% SF6 gas. Optical coherence tomography and functional analysis, including visual acuity test and microperimetry, were performed before surgery and over 3 months. Optical coherence tomography scans revealed macular hole closure at 1-month follow-up. Visual acuity and retinal sensitivity improved from 20/40 to 20/20 and from 13.1 to 14.9 dB, respectively. Fixation stability (bivariate contour ellipse area) improved from 2.02 to 1.58 deg 2 , from 5.44 to 4.24 deg 2 and from 9.72 to 7.58 deg 2 , at 68%, 95%, and 99% of fixation points, respectively., Conclusion: Inverted internal limiting membrane-flap technique may be an alternative approach in patients with full-thickness macular hole complicating diopathic macular telangiectasia type 2, and microperimetry may be a useful tool to analyze related functional changes.

To review challenges in the diagnosis and management of Acanthamoeba keratitis (AK), along with prognostic factors, in order to help ophthalmologists avoid misdiagnosis, protracted treatment periods, and long-term negative sequelae, with an overarching goal of improving patient outcomes and quality of life, we examined AK studies published between January 1998 and December 2019. All manuscripts describing clinical manifestations, diagnosis, treatment, prognosis, and challenges in short- and long-term management were included. The diagnosis of AK is often challenging. An increased time between symptom onset and the initiation of appropriate therapy is associated with poorer visual outcomes. The timely initiation of standardized antiamoebic therapies improves visual outcomes, decreases the duration of treatment, and reduces the chances of needing surgical intervention. In clinical practice, AK diagnosis is often missed or delayed, leading to poorer final visual outcomes and a negative impact on patient morbidity and quality of life.

The cornea actively maintains its own avascular status to preserve its ultimate optical function. This corneal avascular state is also defined as "corneal angiogenic privilege", which results from a critical and sensitive balance between anti-angiogenic and pro-angiogenic mechanisms. In our review, we aim to explore the complex equilibrium among multiple mediators which prevents neovascularization in the resting cornea, as well as to unveil the evolutive process which leads to corneal angiogenesis in response to different injuries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Vision-threatening retinal diseases affect millions of people worldwide, representing an important public health issue (high social cost) for both technologically advanced and new-industrialized countries. Overall RD group comprises the retinitis pigmentosa, the age-related macular degeneration (AMD), the diabetic retinopathy (DR), and idiopathic epiretinal membrane formation. Endocrine, metabolic, and even lifestyles risk factors have been reported for these age-linked conditions that represent a "public priority" also in this COVID-19 emergency. Chronic inflammation and neurodegeneration characterize the disease evolution, with a consistent vitreoretinal interface impairment. As the vitreous chamber is significantly involved, the latest diagnostic technologies of imaging (retina) and biomarker detection (vitreous) have provided a huge input at both medical and surgical levels. Complement activation and immune cell recruitment/infiltration as well as detrimental intra/extracellular deposits occur in association with a reactive gliosis. The cell/tissue aging route shows a specific signal path and biomolecular profile characterized by the increased expression of several glial-derived mediators, including angiogenic/angiostatic, neurogenic, and stress-related factors (oxidative stress metabolites, inflammation, and even amyloid formation). The possibility to access vitreous chamber by collecting vitreous reflux during intravitreal injection or obtaining vitreous biopsy during a vitrectomy represents a step forward for an individualized therapy. As drug response and protein signature appear unique in each single patient, therapies should be individualized. This review addresses the current knowledge about biomarkers and pharmacological targets in these vitreoretinal diseases. As vitreous fluids might reflect the early stages of retinal sufferance and/or late stages of neurodegeneration, the possibility to modulate intravitreal levels of growth factors, in combination to anti-VEGF therapy, would open to a personalized therapy of retinal diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Micera, Balzamino, Di Zazzo, Dinice, Bonini and Coassin.)

Purpose: To investigate clinical and inflammatory changes in the ocular surface of insulin-dependent type I diabetic patients., Methods: Two hundred and nine eyes of 106 patients with diagnosis of type I diabetes were recruited in a prospective observational study. Ocular surface clinical assessment, corneal sensitivity and tear film stability tests were performed to evaluate ocular surface system function. Ocular Surface Disease Index (OSDI) questionnaire was administered to all enrolled subjects. Conjunctival impression cytology specimens were also collected to detect neuromediators and inflammatory molecules. Duration of disease, HbA1c levels and diabetic retinopathy stage were recorded., Results: Corneal sensitivity assessed by Cochet-Bonnet esthesiometer was reduced in patients with more chronic disease, higher HbA1c levels and proliferative diabetic retinopathy. Tear break-up time (TBUT) was reduced in subjects with long-standing diabetes or with more severe retinopathy. OSDI questionnaire scores showed direct correlation with increased HbA1c values. Significant increase of NPY, STAT-5 and ICAM-1 was found in diabetic patients compared to healthy controls. A direct correlation between NPY concentration and ICAM-1 values in patients with type I diabetes was demonstrated., Conclusions: Patients with long-standing type I diabetes showed chronic inflammation of the ocular surface, due to neurogenic dysregulation of para-inflammatory homeostatic mechanisms. These patients with ocular surface system failure complained of ocular discomfort but had modest reduction of corneal sensitivity and no signs of neurotrophic keratopathy. Disease duration, increased HbA1c levels and severe diabetic retinopathy appear the most critical factors., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To compare the safety and the effectiveness of one-port vs. three-port diagnostic vitrectomy in undiagnosed cases of posterior segment inflammation., Methods: We retrospectively collected data from 80 consecutive diagnostic vitrectomies performed using a one-port (n = 40) or a three-port approach (n = 40). Cases of suspected postoperative endophthalmitis were not included in the study. Several variables were compared among groups, including length of surgery, postoperative best-corrected visual acuity (BCVA), diagnostic success and surgical complications., Results: The mean duration of surgery was shorter in the one-port group when compared to the three-port group (15 ± 8 min vs. 49 ± 30; p = 0.0001). The patients were observed for a mean follow-up of 19 months (range 1-84). In the one-port group, the mean BCVA improved from 1.31 ± 0.96 to 0.57 ± 0.59 logarithm of minimum resolution (LogMAR) (p = 0.0009). In the three-port group, BCVA improved from 0.98 ± 0.76 to 0.51 ± 0.76 LogMAR (p = 0.0005). The difference in mean postoperative BCVA between groups was not significative at the last follow-up. One-port vitrectomy yields to a final diagnosis in 80% of the cases, and three-port vitrectomy in 48%. Most of the one-port vitrectomies were carried out under topical anesthesia. After surgery, in both groups three eyes developed a retinal detachment., Conclusions: In this pilot study, the one-port diagnostic vitrectomy has proven to be as effective and safe as the three-port approach, allowing a reduction in surgical times. One-port diagnostic vitrectomy might be considered as the first option for those cases where more complex surgical procedures are not needed.

The extended depth-of-focus intraocular lenses (EDOF IOLs) represent one of the most exciting advancements in the field of lens surgery. EDOF IOLs promise an excellent visual experience, minimizing visual disturbances (ie, halos and glare) commonly associated with multifocal IOLs. The pros and cons of EDOF IOLs should be evaluated in comparison with other more traditional multifocal or monofocal IOLs. The aim of this review is to provide the most current information regarding EDOF IOLs for power calculating formulas, refractive outcomes, incidence of photic phenomena, and patient satisfaction.

Background: Cataract surgery is the most common operation performed worldwide. A fixed topical corticosteroid-antibiotic combination is usually prescribed in clinical practice for 2 or more weeks to treat post surgical inflammation and prevent infection. However, this protracted schedule may increase the incidence of corticosteroid-related adverse events and notably promote antibiotic resistance., Methods: This International, multicentre, randomized, blinded-assessor, parallel-group clinical study evaluated the non-inferiority of 1-week levofloxacin/dexamethasone eye drops, followed by 1-week dexamethasone alone, vs. 2-week gold-standard tobramycin/dexamethasone (one drop QID for all schedules) to prevent and treat ocular inflammation and prevent infection after uncomplicated cataract surgery. Non-inferiority was defined as the lower limit of the 95% confidence interval (CI) around a treatment difference >-10%. The study randomized 808 patients enrolled in 53 centres (Italy, Germany, Spain and Russia). The primary endpoint was the proportion of patients without anterior chamber inflammation on day 15 defined as the end of treatment. Endophthalmitis was the key secondary endpoint. This study is registered with EudraCT code: 2018-000286-36., Results: After the end of treatment, 95.2% of the patients in the test arm vs. 94.9% of the control arm had no signs of inflammation in the anterior chamber (difference between proportions of patients = 0.028; 95% CI: -0.0275/0.0331). No case of endophthalmitis was reported. No statistically significant difference was evident in any of the other secondary endpoints. Both treatments were well tolerated., Conclusions: Non-inferiority of the new short pharmacological strategy was proven. One week of levofloxacin/dexamethasone prevents infection, ensures complete control of inflammation in almost all patients and may contain antibiotic resistance.

Purpose: This focused review aims to explore pediatric non-viral keratitis and to compare associated risk factors, etiologies, antibiotic susceptibilities, empiric treatments and outcomes., Methods: The authors performed a literature research for articles, published on PubMed, Google Scholar, Scopus and Embase online library, relevant to pediatric keratitis etiology, risk factors, antibiotic susceptibilities, treatment and outcomes. From the bibliography of selected articles, additional relevant articles were also considered. Of 34 articles identified, 21 were suitable for the purpose of this review., Results: Several risk factors are noted in the field of pediatric keratitis. Trauma is the most common in developing countries, while contact lenses wear is seen in developed economies. Previous ocular conditions and systemic diseases also contribute. Associated malnourishment and vitamin A deficit are fraught with a catastrophic prognosis. Among causative organisms, bacteria are more common than fungi and protozoa. Gram-positive organisms are predominant where contact lenses use is infrequent. Pseudomonas aeruginosa is often the leading pathogen in developed countries and is strongly associated with contact lens wear or malnourishment. Fungi are common in the tropics and associated with trauma. Levofloxacin seems the more effective empirical treatment when bacteria are suspected, but there is no agreement on a standard of care., Conclusion: There are differences in etiologic patterns between developing and developed countries and different regions globally. Risk factors follow the same trend; however, there is no standard regimen being followed for empirical treatment of pediatric infectious keratitis. Associated malnourishment and vitamin A deficiency result in poorer outcomes.

Purpose: To evaluate, by laser photometry, the persistency of anterior chamber flare after uneventful phacoemulsification in asymptomatic patients with no signs of inflammation on slit lamp examination., Method: Seventy-five patients previously enrolled in a randomized clinical trial that evaluated inflammation after uneventful phacoemulsification in eyes treated with dexamethasone 0.1% ophthalmic suspension (group 1) or bromfenac 0.09% ophthalmic solution (group 2) for 2 weeks. Anterior chamber inflammation was investigated by laser flare photometry. At 30 days after surgery, laser flare showed persistently elevated values. For this reason, patients were further analyzed at 3 and 6 months. Additionally, optical coherence tomography was used to measure the central macular thickness (CMT) and to assess for postoperative pseudophakic macular edema., Results: When compared to preoperative values, laser flare photometry demonstrated persistent ocular inflammation at postoperative days 90 and 180 in group 1, but not in group 2. Laser flare values showed a significant reduction in group 2 compared to group 1 throughout all the follow-up (p < 0.001). The increase in mean CMT at days 90 and 180 with respect to baseline was statistically significant in group 1 but not in group 2, in which it decreased to levels similar to preoperative value. Group 1 showed a higher increase in mean CMT compared to group 2 throughout all the follow-up (p < 0.001). The proportion of patients that developed pseudophakic cystoid macular edema (CME) was 14% (n = 5) and 0% (n = 0) in group 1 and group 2, respectively (p = 0.02). The bivariate analysis demonstrated a positive correlation between laser flare and CMT values in group 1 but not in group 2., Conclusion: Anterior chamber inflammation persists for more than 30 days in a significant proportion of patients after uncomplicated cataract surgery and may be responsible for late onset of cystoid macular edema cases., Trial Registration: ClinicalTrials.gov identifier, NCT03317847.