Demodex blepharitis is a chronic inflammatory ocular condition caused by Demodex mite infestation of the eyelid that can negatively impact quality of life. Currently, lotilaner ophthalmic solution 0.25% is the only FDA-approved treatment for Demodex blepharitis. The Demodex Expert Panel on Treatment and Eyelid Health has established consensus that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis. We report a patient who presented with collarettes, the pathognomonic sign of Demodex blepharitis, meibomian gland dysfunction, and poor visual acuity. The patient also had a history of neovascular age-related macular degeneration. Consistent with the Demodex Expert Panel on Treatment and Eyelid Health consensus recommendations, the patient was treated with lotilaner ophthalmic solution 0.25%, lid scrubs, and warm compresses. At the 2-month follow-up, collarettes had resolved, and signs of meibomian gland dysfunction had improved. This case supports the Demodex Expert Panel on Treatment and Eyelid Health recommendation that lotilaner ophthalmic solution 0.25% should be considered the preferred first-line treatment for Demodex blepharitis.
Introduction:Demodex blepharitis (DB) is a chronic ocular inflammation caused by Demodex mite infestation of the eyelid. DB is often misdiagnosed, as some of its clinical findings and patient-reported outcomes overlap with those of other ocular surface diseases. The Demodex Expert Panel on Treatment and Eyelid Health (DEPTH) has reached consensus on the symptomatology, diagnosis, and treatment of DB. Consensus findings from the DEPTH group include that collarettes are pathognomonic for DB and that lotilaner ophthalmic solution, 0.25%, the first and only FDA-approved treatment for DB, should be the first-line treatment for the disease. This case series highlights two instances of misdiagnosis that were subsequently re-evaluated using consensus findings from the DEPTH group, leading to a correct diagnosis and effective treatment with XDEMVY® (lotilaner ophthalmic solution) 0.25%. Case Reports:Two cases of patients with DB are presented. In the first case, a 75-year-old female presented with collarettes, reduced meibomian gland secretions, and lid margin erythema. After an unsuccessful initial treatment for bacterial infection, the patient was diagnosed with DB and prescribed lotilaner ophthalmic solution, 0.25% twice daily for 6 weeks, which improved all clinical findings and patient-reported outcomes. In the second case, a 62-year-old male presented with ocular discomfort, dry eye, and burning and itching sensations. After an unsuccessful initial treatment for dry eye disease, collarettes were detected, and the patient was diagnosed with DB. Subsequent treatment with lotilaner ophthalmic solution, 0.25% reduced collarettes and resolved patient-reported symptoms. Conclusion:These cases highlight patients with DB who were initially misdiagnosed and eventually treated with lotilaner ophthalmic solution, 0.25%. Each case exemplifies the utility of the DEPTH consensus findings in improving the diagnostic path for patients and eye care providers. Future case series from other groups will continue to shed light on the best practices for diagnosing and treating patients with DB.
A safe and effective treatment for chronic ocular surface pain (COSP) remains an unmet need. This prospective feasibility study investigated the impact of an ophthalmic cooling device (ETX-4143) on ocular pain, as well as corneal nerve and immune cell features, in individuals with COSP. For this clinical trial (Clinicaltrials.gov:NCT07059754), the more symptomatic (study) eye was treated with the ETX-4143 device, involving two metallic probes, internally cooled by a −20 °C fluid, applied to the bulbar conjunctiva posterior to the limbus at 3 and 9 o’clock for 4 min, with a fellow (untreated) eye control. Ocular pain, best-corrected visual acuity (BCVA), tear osmolarity, corneal sensitivity, slit lamp biomicroscopy, ocular surface staining, and static and functional in vivo confocal microscopy (Fun-IVCM) were conducted at baseline and 2-, 6-, and 12-weeks posttreatment. Corneal nerve and immune cell parameters were quantified. Five eligible participants were enrolled and completed the study (mean age 66.4 ± 9.9 years, 60
ABSTRACT Purpose Fuchs endothelial corneal dystrophy (FECD) is a progressive disease, causing premature death of corneal endothelial cells (CECs). Iron-dependent lipid peroxidation and ferroptosis mediate cell death in FECD. We aimed to determine whether FECD progression is mediated by derangements in ferritinophagy – a form of autophagy that degrades ferritin to release labile ferrous iron – and whether ultraviolet A (UVA) exposure drives FECD progression by activating ferritinophagy. Methods Endothelium-Descemet membrane (EDM) tissues were collected from patients with end-stage FECD undergoing endothelial keratoplasty and from healthy age-matched donor corneas. Separately, immortalized FECD and healthy control CEC lines were cultured. Cellular levels of NCOA4 production and LC3 activation, both markers of ferritinophagy, were quantified using western blotting and PCR. UVA-exposed immortalized cells were plated on coverslips, stained for immunohistochemistry (IHC), and analyzed using confocal microscopy. Corneal endothelial peels were stained and analyzed using laser ablation–inductively coupled plasma–mass spectrometry (LA-ICP-MS). Results Surgically explanted FECD CECs showed significantly increased levels of NCOA4 compared to healthy controls. LC3 activation was increased in FECD immortalized CECs; UV exposure further increased LC3 activation. Additionally, UVA exposure showed trends of increased expression of NCOA4 in immortalized FECD and healthy CECs. On IHC of FECD surgical explant tissue, ferritin was decreased markedly, NCOA4 localized in a dramatic punctate pattern, and both ferritin and LC3 localized within cell nuclei. Spectrometry images showed higher iron levels correlating with areas of higher FECD disease burden. Conclusions Our results demonstrate ferritinophagy in FECD indicated by the increase of NCOA4 and LC3 ferritinophagy markers in FECD patient and cell culture models. Our finding that UVA activates ferritinophagy implicates this mechanism in UVA-mediated FECD progression. Altogether, aberrant iron dysregulation associated with FECD and ferroptosis may be mediated by ferritinophagy, providing a biomarker to assess disease severity as well as a potential target for future medical therapeutics.
