Impact of Upadacitinib on Atopic Keratoconjunctivitis Exacerbated by Dupilumab Treatment in Atopic Dermatitis Patients: A Prospective Dermatological and Ophthalmological Clinical Evaluation in Common Clinical Practice.

Introduction: Atopic dermatitis (AD) is a prevalent chronic inflammatory skin condition with a substantial impact on patients, particularly due to ocular involvement known as atopic keratoconjunctivitis (AKC). Current therapeutic approaches, such as dupilumab, often lead to conjunctivitis, prompting exploration of alternative treatments like upadacitinib. Methods: We collected dermatological and ophthalmological prospective clinical evaluations of six adults with moderate-to-severe AD, undergoing treatment with upadacitinib after discontinuation of dupilumab due to the onset of AKC during therapy and the worsening of dermatitis in particular in the head and neck region. Clinical evaluations, including EASI scores, itch and sleep NRS, DLQI, and ocular parameters, were performed at baseline (during screening assessment before switching to upadacitinib) and then at week 12 and week 24. Clinical evaluation of AKC was performed by a team of ophthalmologists. Results: Upadacitinib not only improved atopic dermatitis in terms of EASI, itching, and sleep NRS, but also demonstrated a notable reduction in ocular signs and symptoms, as indicated by the Visual Analogue Scale (VAS), the Efron scale, and the Ocular Surface Disease Index Symptom Severity (OSDISS) scores. Discussion: Our observation of common clinical practice underscores the substantial impact of biological and small-molecule therapies on AD, emphasizing the limitation posed by dupilumab-associated conjunctivitis. Switching to upadacitinib significantly improved both clinical and functional ocular outcomes, suggesting its potential as an alternative therapeutic option for AD patients with ocular involvement. Conclusion: The presented data provides insights into the complex interplay between systemic therapies and ocular manifestations in AD. Upadacitinib emerges as a promising option to address dupilumab-associated conjunctivitis, offering improved quality of life for patients.

Customized Scleral Lenses: An Alternative Tool for Severe Dry Eye Disease-A Case Series.

Purpose: Dry eye disease (DED) is a multifactorial condition significantly impacting patients' quality of life (QoL). This study aims to present a case series highlighting the effectiveness of customized scleral lenses in managing severe DED and improving patient outcomes. Methods: This case series includes three patients with severe DED refractory to conventional treatments. Customized scleral lenses were fitted for each patient, and clinical outcomes were evaluated over a period of two months. Assessments included best-corrected visual acuity (BCVA), slit-lamp examination findings, and corneal National Eye Institute (NEI) scores. Results: All three patients demonstrated significant improvements in BCVA, reductions in ocular symptoms, and enhanced ocular surface health. Patient 1, with secondary Sjögren's syndrome and suspected mucous membrane pemphigoid, showed resolution of conjunctival hyperemia and epithelial defects. Patient 2, with graft versus host disease, exhibited resolution of punctate keratitis and the absence of thread mucus. Patient 3, post-oncologic surgery, achieved complete resolution of keratoconjunctivitis sicca and the restoration of vision. Conclusions: Customized scleral lenses are a useful therapeutic option for severe DED, providing significant symptomatic relief and enhancing patients' quality of life. Their use should be considered in refractory cases to optimize ocular surface health and visual outcomes.

Dupilumab-associated ocular surface disease or atopic keratoconjunctivitis not improved by dupilumab? Upadacitinib may clarify the dilemma: A case report.

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.

A Functional and Immunologic Point of View on Corneal Endothelial Transplantation: A Systematic Review and Meta-Analysis.

Background: To systematically review and meta-analyze the immunologic aspects and outcomes of various endothelial keratoplasty (EK) techniques, specifically comparing Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK), Ultra-Thin Descemet's Stripping Automated Endothelial Keratoplasty (UT-DSAEK), and Descemet's Membrane Endothelial Keratoplasty (DMEK). Methods: Systematic review and meta-analysis. Main outcomes were the proportion of patients achieving a best spectacle-corrected visual acuity (BSCVA) of 20/20 at 6 months after keratoplasty, rejection rate one year after surgery, BSCVA at last follow up, and postoperative immunomodulating regimen. Results: A higher proportion of DMEK patients achieved a BSCVA of 20/20 after 6 months. UT-DSAEK and DMEK showed similar rejection rates with a lower risk of re-bubbling for UT-DSAEK (4% vs. 20%). Conclusions: DMEK showed faster visual recovery than UT-DSAEK but a similar rejection rate and long-term visual acuity. One-year postoperative slow tapering steroid regimen has a positive but not (yet) significant effect on rejection risk and visual outcomes.

Mast cells and ocular surface: An update review.

Mast cells (MCs), traditionally viewed as key players in IgE-mediated allergic responses, are increasingly recognized for their versatile roles. Situated at critical barrier sites such as the ocular surface, these sentinel cells participate in a broad array of physiological and pathological processes. This review presents a comprehensive update on the immune pathophysiology of MCs, with a particular focus on the mechanisms underlying innate immunity. It highlights their roles at the ocular surface, emphasizing their participation in allergic reactions, maintenance of corneal homeostasis, neovascularization, wound healing, and immune responses in corneal grafts. The review also explores the potential of MCs as therapeutic targets, given their significant contributions to disease pathogenesis and their capacity to modulate immunity. Through a thorough examination of current literature, we aim to elucidate the immune pathophysiology and multifaceted roles of MCs in ocular surface health and disease, suggesting directions for future research and therapeutic innovation.

Prophylactic Therapy for Long-Term Ocular Discomfort After Cataract Surgery.

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.

Novel Effective Medical Therapy for Acanthamoeba Keratitis.

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.

Ocular Surface Disease as Extraesophageal Gastroesophageal Reflux Disease Manifestation: A Specific Therapeutic Strategy.

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.

HYPERACUTE PSEUDOPHAKIC MACULAR EDEMA VANISHING WITHIN 72 HOURS: A CASE SERIES.

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.

Microperimetric evaluation and predictive factors of visual recovery after successful inverted internal limiting membrane-flap technique for macular hole in high myopic eyes.

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 (ß = 0.60, p = 0.02) and RS (ß = -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.

Tissue Remodeling in Ocular Mucous Membrane Pemphigoid.

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-ß), 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.

Biofeedback Training after Successful Inverted Internal Limiting Membrane (ILM)-Flap Technique for High Myopic Macular Hole.

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.

Promising High-Tech Devices in Dry Eye Disease Diagnosis.

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.

Ocular surface in posterior segment surgery.

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.

Meningococcal Conjunctivitis in a 54-Year-Old Man: Case Report and Review of the Literature.

Neisseria meningitidis represents an uncommon pathogen of acute bacterial conjunctivitis. In this brief report, we describe a case of meningococcal conjunctivitis in an immunocompetent adult male, with a review of the literature. The patient went to the outpatient ophthalmology clinic complaining of severe ocular discomfort, burning, and redness for more than 2 weeks and, at slit lamp examination, he was diagnosed with a mild conjunctivitis. Microbiology cultures of ocular swabs revealed the growth of colonies, as pure culture, identified as N. meningitidis of serogroup B. A diagnosis of primary meningococcal conjunctivitis was made and treatment of patient with intramuscular injections of ceftriaxone in addition to topical moxifloxacin eye drops for 2 weeks led to clinical improvement and, finally, to a complete recovery, in accordance with microbiological findings. Ophthalmologists must be aware of the possibility of primary meningococcal conjunctivitis cases, even uncommon, and the need to treat with systemic antibiotics and their close contacts with adequate antibiotic chemoprophylaxis.

Inflammation and Dry Eye-like Symptoms as Concomitant Manifestations of Laryngo-Pharyngeal Reflux.

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.

Real Life Impact of Dry Eye Disease.

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.

Ex Vivo Evaluation of a Pressure-Sensitive Device to Aid Big Bubble Intrastromal Dissection in Deep Anterior Lamellar Keratoplasty.

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.

Tissue remodeling in adult vernal keratoconjunctivitis.

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 (TGFß1,2,3 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 TGFß were higher in adult VKC group. Significantly higher levels of TGFß3 (3.44 ± 1.66; p < 0.05) were detected in adult VKC compared to childhood VKC, associated with an increasing trend of TGFß1 (1.58 ± 0.25) and TGFß2 (1.65 ± 0.20) isoforms levels. Molecular analysis showed a relative increase in tissue remodeling/fibrogenic transcripts (TGFß 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 TGFß 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.