Vernal keratoconjunctivitis in adults: a narrative review of prevalence, pathogenesis, and management.

Vernal keratoconjunctivitis (VKC) is a chronic, progressive, allergic ocular surface disorder that can lead to sight-threatening complications. VKC occurs primarily in children and generally resolves about the time of puberty; however, case series and retrospective analyses indicate that approximately 10% of patients with VKC are adults, and that a subset of adult cases develop after puberty. Consequently, two age-related variants of VKC have recently been described: early-onset VKC-which manifests during childhood and persists into adult life-and late-onset disease, which emerges de novo after puberty. Although the signs and symptoms of adult and childhood VKC are similar, adult VKC is a long-lasting disease characterized by severe inflammation and increased risk of conjunctival fibrosis, which may place adult patients at higher risk for sight-threatening complications and adverse impacts on daily life. This review discusses the epidemiology, signs, symptoms, immunopathogenesis of adult VKC variants, and highlights current gaps in research and management of patients with this condition.

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.

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.

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.

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.

Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation.

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high-risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo-controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in ≥ 1 quadrants of the corneal graft and host bed, excluding the limbus. Methods: Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure, followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure, followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main Outcome Measures: Vessel and invasion area of vessels in the corneal graft and host beds. Results: This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment groups. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years, and the mean age of those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72% ± 3.19%) and control groups (15.48% ± 3.12%; P = 0.72). Similarly, the invasion areas were also similar in the treatment (35.60% ± 2.47%) and control (34.23% ± 2.64%; P = 0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab-treated group (83.7%) over a period of 52 weeks compared with the control group (61.5%; P < 0.0001). In the bevacizumab-treated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure in cases of first (3.54% ± 1.21%) and repeat (3.80% ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle-treated patients, the vessel area was significantly higher in repeat (9.76% ± 0.32%) compared with first (8.06% ± 1.02%; P < 0.0001) penetrating keratoplasty. In the bevacizumab treatment group, invasion areas at week 52 were comparable in first (11.70% ± 3.38%) and repeat (11.64% ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87% ± 2.57%) as compared with first (24.11% ± 2.17%) penetrating keratoplasty in vehicle-treated patients. Conclusions: In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

One Soul and Several Faces of Evaporative Dry Eye Disease.

The ocular surface system interacts with, reacts with, and adapts to the daily continuous insults, trauma, and stimuli caused by direct exposure to the atmosphere and environment. Several tissue and para-inflammatory mechanisms interact to guarantee such an ultimate function, hence maintaining its healthy homeostatic equilibrium. Evaporation seriously affects the homeostasis of the system, thereby becoming a critical trigger in the pathogenesis of the vicious cycle of dry eye disease (DED). Tear film lipid composition, distribution, spreading, and efficiency are crucial factors in controlling water evaporation, and are involved in the onset of the hyperosmolar and inflammatory cascades of DED. The structure of tear film lipids, and subsequently the tear film, have a considerable impact on tears' properties and main functions, leading to a peculiar clinical picture and specific management.

Uncommon Blepharitis.

Blepharitis is a common chronic inflammatory condition affecting the eyelid margins; the pathophysiology of blepharitis is complex and not fully understood. The disease is anatomically divided into anterior (inflammation of eyelashes) and posterior (meibomian gland dysfunction) types. Diagnosis relies on clinical examination, revealing characteristic features like scurf, vascular changes, and meibomian gland dysfunction. The main goals of blepharitis treatment are symptom relief, recurrence prevention, and complication risk minimization. Treatment options include lid hygiene, topical and systemic antibiotics, topical corticosteroids, and omega-3 supplements. However, it is important to highlight reported cases of blepharitis as side effects of systemic therapies, particularly in the context of chemotherapy, bortezomib, cetuximab, TNFα inhibitors, and dupilumab. It is crucial to monitor patients undergoing such treatments regularly and attentively in order to promptly set up adequate supportive therapy. Of even more importance is future research on the pathophysiological mechanisms responsible for the occurrence of these ocular side effects in order to find a nosological cure for the issue.

Preventing and Managing Iatrogenic Dry Eye Disease during the Entire Surgical Pathway: A Study Focusing on Patients Undergoing Cataract Surgery.

Patient expectations for cataract surgery are continuously increasing, and dry eye disease (DED) represents a major cause of patient dissatisfaction in eye surgery. The present opinion paper aims to provide useful insights to improve the entire pathway of a patient undergoing cataract surgery, from the preoperative setting to the postoperative one. The available evidence from main clinical trials published on this topic is presented in association with experience-based points of view by the authors. Ocular surface disease (OSD) is common in patients presenting for cataract surgery, and more than half of these patients have DED and meibomian gland dysfunction (MGD), even in the absence of symptoms. Therefore, there is a need to encourage preoperative assessments for the risk of DED development or worsening in all patients as a routine approach to cataract surgery. New all-in-one diagnostic machines allow for fast and noninvasive screening of the ocular surface status. Once a preoperative diagnosis of DED/OSD is reached, ocular surface optimization should be obtained before surgery. In the case of unresolved OSD, the decision to delay surgery should be considered. The surgical procedure can be optimized by avoiding large incisions, limiting microscope light intensity and exposure, and avoiding an aspirating speculum or preserved eye drops. Postoperatively, the continued avoidance of preserved agents is advisable, as well as a limited exposure to epitheliotoxic antibiotics and nonsteroidal anti-inflammatory drugs. Short-term, preservative-free, soft corticosteroids may be useful for patients with extensive or persistent inflammation.

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.

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.

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.

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.

A review on drug-induced dry eye disease.

Dry eye disease encompasses a broad range of etiologies and disease subtypes which have similar clinical manifestations. Medications can cause dry eye disease or symptoms of dryness as a side effect by either interfering with the lacrimal gland or meibomian gland function, or both, and by other mechanisms that affect the ocular surface homeostasis. This is important to know and recognize as eliminating the offending medication can reverse the symptoms and, in many cases, prevent further deterioration of the ocular surface inflammation. This review focuses on drugs like systemic isotretinoin and taxanes, which cause meibomian gland dysfunction; immune checkpoint inhibitors that cause lacrimal gland dysfunction; gliptins and topical antiglaucoma medications that cause cicatrizing conjunctivitis; and epidermal growth factor receptor inhibitors, fibroblast growth factor receptor inhibitors, and belantamab mafodotin, which cause mucosal epitheliopathy. Many of these medications, particularly the newer anticancer agents, have only recently been introduced for clinical use, and knowledge and awareness of their ocular side effects are still evolving. This review aims to update ophthalmologists on the drug-induced causes of dry eye disease or symptoms of dryness, which is avoidable by discontinuation of the incriminating agent or can be mitigated by reducing the dose or frequency of usage.