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Purpose: Antibody-drug conjugates (ADCs) are a relatively recent advance in the delivery of chemotherapeutics that improve targeting of cytotoxic agents. However, despite their antitumor activity, severe ocular adverse effects, including vision loss, have been reported for several ADCs. The nonspecific uptake of ADCs into human corneal epithelial cells (HCECs) and their precursors via macropinocytosis has been proposed to be the primary mechanism of ocular toxicity. In this study, we evaluated the ability of a novel polymer, poly(l-lysine)–graft–poly(ethylene glycol) (PLL-g-PEG), to decrease the ADC rituximab-mc monomethylauristatin F (MMAF) (RIX) uptake into human corneal epithelial (HCE-T) cells. Methods: HCE-T cells were exposed to increasing concentrations of RIX to determine inhibition of cell proliferation. HCE-T cells were treated with PLL-g-PEG, the macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA), or vehicle. After 30 min of incubation, RIX was added. ADC was detected by fluorescent anti-human immunoglobulin G and fluorescently conjugated dextran as viewed by microscopy. Results: RIX caused dose-dependent inhibition of HCE-T cell proliferation. EIPA significantly reduced RIX uptake and decreased macropinocytosis as assessed by direct quantification of RIX using a fluorescently conjugated anti-human antibody as well as quantification of macropinocytosis using fluorescently conjugated dextran. PLL-g-PEG resulted in a dose-dependent inhibition of RIX uptake with half-maximal inhibitory concentrations of 0.022%–0.023% PLL-g-PEG. Conclusion: The data show PLL-g-PEG to be a potent inhibitor of RIX uptake by corneal epithelial cells and support its use as a novel therapeutic approach for the prevention of ocular adverse events associated with ADC therapy. [ABSTRACT FROM AUTHOR]

Neurotrophic keratopathy is an uncommon degenerative corneal disorder characterized by compromised corneal sensory innervation resulting in the formation of epithelial defects and nonhealing corneal ulcers. Various treatment modalities are available to stabilize disease progression, improve patient well-being, and prevent vision loss. For eligible patients, medical and surgical reinnervation have emerged as pioneering therapies, holding promise for better management. We present a comprehensive review of the disorder, providing an update relevant to ophthalmologists on pathogenesis, diagnosis, treatment options, and novel therapies targeting pathophysiological pathways. [ABSTRACT FROM AUTHOR]

The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13 years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15 years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101 patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041 patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3 years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date. [ABSTRACT FROM AUTHOR]

Objective: To survey the prevalence of pathogens in shelter‐housed cats with active ocular surface disease (OSD). Animals Studied: A total of 255 shelter‐housed domestic cats with evidence of active OSD. No normal, unaffected cats were sampled. Procedure(s): OSD scoring was performed on cats with active OSD. Combined oropharyngeal/conjunctival swabs were submitted for rt‐PCR/PCR for feline herpesvirus (FHV‐1), feline calicivirus (FCV), Chlamydia spp. (CHL), Bordetella bronchiseptica (BORD), and Mycoplasma spp. (MYC). Results: Pathogens were detected as follows: 76.4% (195/255) MYC, 57.6% (147/255) FHV‐1, 42.7% (109/255) FCV, 26.7% (68/255) CHL, and 5.5% (14/255) BORD. Monoinfections affected 21.1% (54/255) animals, with MYC being the most common monoinfection (12.5%, 32/255), followed by FHV‐1 (4.7%, 12/255), followed by CHL (2.4%, 6/255), followed by FCV (1.6%, 4/255), with no animals having a BORD monoinfection. Dual infections affected 36.4% of animals (93/255), with MYC detected in 30.1% (77/255) dual infections and FCV detected in 12.9% (33/255) dual infections. Dual infections with MYC and FCV together were detected in 9.8% (25/255) animals. Many animals (35.3%, 90/255) were found to be affected by 3 or more pathogens, and 7.1% (18/255) animals had no pathogens detected. OSD scores were not influenced by any variable assessed, including the number and type of pathogens detected. Conclusion: MYC, FHV‐1, FCV, and CHL were commonly detected in this group of animals with OSD. Both MYC and FCV (alone or in combination with each other) were detected in multiple animals with active OSD, supporting prior evidence that either may independently act as a primary ocular surface pathogen. [ABSTRACT FROM AUTHOR]

Background: Ocular surface (OS) disorders before glaucoma filtration surgery (GFS) have been considered to play a crucial role influencing the surgical outcome. Conversely, the impact of surgery itself on the OS is almost completely overlooked, though evidence suggest that ocular surface disease (OSD) may be induced in patients by GFS. This review analyzes the determinants involved in the OSD development after GFS, the clinical features and related consequences, the main diagnostic hallmarks, as well as the therapeutic strategies for its management. Methods: The PubMed database was utilized for the literature examination. Keywords that were searched included ocular surface disease, glaucoma filtration surgery, filtration bleb, post-surgical management, and quality of life. Results: After GFS, OSD is promoted by peri- and post-operative factors, such as the filtration bleb (FB) development, combined surgical approach with phacoemulsification, the use of antifibrotic agents and the reintroduction of antiglaucoma medications. This particular form of OSD that present similar clinical features to mild to moderate dry eye, can be named as post-glaucoma surgery-OSD (PGS-OSD). PGS-OSD may negatively affect the FB functionality, thus potentially hindering the disease control, and significantly worsen the patient quality of life (QOL). Conclusions: Clinicians are encouraged to routinely include the OS evaluation after GFS and to consider proper management when the occurrence of PGS-OSD worsen the patient's QOL or exert negative effects to the FB functionality. An outline summarizing the main risk factors and the most appropriate therapeutic options to mitigate the PGS-OSD was proposed to support the routine practice. [ABSTRACT FROM AUTHOR]

Saif Khuzaim Al-Dossary Ophthalmology Consultant, King Faisal University, Al-Ahsa, Saudi ArabiaCorrespondence: Saif Khuzaim Al-Dossary, Email Saldossari@kfu.edu.saObjective: This cross-sectional study aimed to investigate the associations between environmental and occupational factors and the prevalence of dry eye symptoms among participants from the Ahsa region of Saudi Arabia.Methods: Participants from urban, rural, and suburban areas seeking medical care at primary health centers were recruited through systematic random sampling. Data on demographics, exposures, and ocular health were captured using a structured questionnaire. Dry eye symptoms were evaluated using the Ocular Surface Disease Index (OSDI), Impact of Dry Eye on Everyday Life (IDEEL), and Symptom Assessment in Dry Eye (SANDE) questionnaires. Logistic regression analysis examined the relationships between environmental/occupational factors and the prevalence of dry eye symptoms.Results: Key exposures included particulate matter (PM) (60%), low humidity (55%), wind/dust (50%), prolonged computer use (65%), and chemical irritants (45%). These factors were significantly associated with an increased prevalence of dry eye symptoms, with the following odds ratios (ORs): PM (1.85, 95% CI: 1.35– 2.52), low humidity (1.45, 95% CI: 1.05– 2.00), wind and dust (1.60, 95% CI: 1.20– 2.14), prolonged computer use (2.10, 95% CI: 1.55– 2.85), and chemical irritants (1.75, 95% CI: 1.30– 2.35). All associations were statistically significant (p < 0.05). The use of protective equipment was associated with reduced odds of dry eye symptoms (OR 0.60, 95% CI: 0.42– 0.85, p = 0.03).Conclusion: This study identifies significant associations between specific environmental and occupational exposures and the prevalence of dry eye symptoms. Reducing modifiable exposures through policy, workplace enhancements, and clinical preventative strategies is essential to mitigate the burden of dry eye symptoms related to modern lifestyles and technology.Keywords: ocular surface disease, air pollution, low humidity, digital eye strain, occupational hazard

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Abstract The LipiFlow Thermal Pulsation System received its first marketing clearance for the treatment of meibomian gland dysfunction (MGD) 13 years ago. Since then, the evidence evaluating the effectiveness and safety of LipiFlow as a treatment for MGD has grown significantly. The objective of this comprehensive review was to summarize all clinical reports evaluating the effectiveness and safety of LipiFlow over the past 15 years. The literature was systematically reviewed, and 55 unique articles had subjective (patient-reported outcomes) and objective (meibomian gland function, tear production, and ocular staining) outcomes for extraction. Data were collected from 2101 patients and 3521 eyes treated with LipiFlow. Of these, effectiveness was evaluated in 2041 patients and 3401 eyes, and safety was evaluated in 1448 patients and 2443 eyes. Taken together, the studies demonstrate that a single 12-min treatment with LipiFlow safely improves signs and symptoms of MGD and associated evaporative dry eye disease (DED), and the benefits persist up to 3 years in some cases. The findings are corroborated by multiple meta-analyses and consensus guidelines. While some studies showed that daily eyelid hygiene, warm compress, and/or massage had a similar benefit to a single LipiFlow, these treatments were limited by inconvenience, discomfort, and non-compliance. The majority of studies evaluating safety reported no discomfort or pain associated with LipiFlow treatment, which supports the patient acceptability of LipiFlow therapy. All adverse events (AEs) related to LipiFlow were transient, non-vision-threatening, and did not require treatment. No studies reported serious AEs. The data obtained from 55 studies conducted globally overwhelmingly show that LipiFlow is effective and safe for the treatment of MGD and associated evaporative DED. The conclusions are supported by the diversity of the patient populations (geography, race, disease severity, and diagnosis), the large population treated with LipiFlow, the meta-analyses, and that this review analyzed all published clinical studies to date.

Francesco Oddone,1 Lucia Tanga,1 Sara Giammaria,1 Lorenzo Sabbatini,2 Alfonso Strianese,2 Manuela Ferrazza,1 Luca Mario Rossetti2 1IRCCS - Fondazione Bietti, Rome, Italy; 2Eye Clinic, ASST Santi Paolo E Carlo, University of Milan, Milan, ItalyCorrespondence: Francesco Oddone, Glaucoma Unit IRCCS Fondazione Bietti, Via Livenza 3, Roma, 00198, RM, Italy, Tel +39-06-85356727 ; +39-3291921575, Email odd1fr@gmail.comPurpose: The effectiveness, safety and tolerability of the preservative-free fixed combination of tafluprost and timolol (PF-TTFC) were evaluated over the 24-h in patients with open-angle glaucoma or ocular hypertension showing signs and symptoms of Ocular Surface Disease (OSD) and uncontrolled intraocular pressure (IOP) on prior benzalkonium chloride (BAK) – Latanoprost monotherapy.Methods: In this multi-center, prospective, interventional, non-comparative clinical trial, patients treated with BAK-Latanoprost underwent 24-h IOP measurements (8 am, 11 am, 2 pm, 5 pm, 8 pm, 11 pm, 2 am, 5 am) at baseline and after 3 months from switch to PF-TTFC. Mean 24-h IOP and daytime (8 am– 8 pm) vs nighttime (11 pm – 5 am) IOP were compared. Changes in OSD signs and symptoms, quality of life (QoL) and in-vivo corneal confocal microscopy (IVCM) were also evaluated.Results: Thirty-eight patients were analyzed. The mean 24-h IOP significantly decreased after 3 months from 17.8 mmHg (95% CI: 17.1– 18.6) to 15.3 mmHg (95% CI: 14.6– 16.1, p < 0.001). IOP was significantly reduced both at daytime (p < 0.001) and nighttime (p < 0.001), with better IOP control at night [− 2.9 (95% CI: − 3.5 to − 2.1) mmHg vs − 2.3 (95% CI: − 2.9 to − 1.6) mmHg]. In 20 patients (52.6%), corneal fluorescein staining improved, whereas in 4 patients (10.5%) it worsened. Hyperemia has improved in 24 (63.3%) patients and worsened in 2 (5.3%). Breakup time, Schirmer test and QoL scores showed no changes. At IVCM, the mean corneal wing-cell size was found significantly decreased (p < 0.005).Conclusion: The switch from BAK-Latanoprost to PF-TTFC significantly reduced IOP over the 24-h and improved OSD signs and symptoms.Keywords: glaucoma, tafluprost-timolol fixed combination, preservative free, BAK, prostaglandins, 24-h effectiveness, ocular surface disease

Background: Ocular involvement in autoimmune bullous dermatoses (AIBD) remains underappreciated. Objectives: The objective was to study the prevalence and characteristics of ocular involvement in patients with AIBD. Methods: The medical records of 25 patients (males: females 11:14) aged between 27 and 85 years (mean ± standard deviation = 44.9 ± 15.6 years) with AIBD were analyzed retrospectively for clinico-epidemiological attributes and the presence of ocular abnormalities. Results: There were 20 (80%) pemphigus patients, of which most were pemphigus vulgaris (PV, n = 14) and pemphigus foliaceus (PF, n = 6). Other 5 (20%) patients included bullous pemphigoid (BP, n = 4) and cicatricial pemphigoid (CP, n = 1). Seventeen (68%) patients comprising 11 (78.6%) of PV, 3 (50%) of PF, 2 (50%) of BP, and 1 (100%) of CP had 27 ocular abnormalities. Erosions of lid margins (n = 3, 27.3%), blepharitis with meibomitis (n = 1, 9.1%), chalazion (n = 1, 9.1%), and conjunctival vesicles over bulbar conjunctivae (n = 2, 18.2%), conjunctivitis (PV = 5, 45.5%, PF = 1, 33.3%), and symblepharon and keratoconjunctivitis sicca in one (9.1%) patient each, respectively, were major ocular manifestations in pemphigus. Entropion with trichiasis, shallow fornices, and corneal opacities were major abnormalities in patients with BP (n = 2, 100%) and CP (n = 1, 100%). Conclusion: Ocular comorbidities vary in prevalence and severity between subtypes of AIBD. These are mainly from complications of ocular surface disease predominantly affecting the anterior segment of the eye. They are more severe in patients with CP compared to others. The study is limited by a single-center, retrospective-study design, a small number of patients in each group for stratification, and long-term follow-up.

Abstract Background The use of povidone-iodine for ocular surface asepsis is widespread for intravitreal injections. They became frequent procedures, leading to serial exposure of patients’ eyes to iodinated solutions. In this study, we investigate the changes in the ocular surface in patients submitted to repeated use of povidine for intravitreal injection of anti-VEGF asepsis, analyzing Ocular Surface Disease Index, non-invasive break up time, blinking quality, lipid layer, meniscus height and osmolarity. Methods This case-control study included 34 individuals (68 eyes), 14 males, 20 females aged 48 to 94. Inclusion criteria were individuals who received application of 2% povidone-iodine eyedrops for intravitreal injections treatment with the non-treated contralateral eye used as control. Ocular surface examinations were performed at a single occasion. A pre-intravitreal injection asepsis protocol with povidone-iodine was applied. All statistical analysis was performed using the STATA® 18.0 Software and a p-value = 0.05 was considered as the statistical significance value in all tests. Results The median number of IVIs in treated eyes was 12 (range 6–20). The results in treated eyes compared with untreated eyes were respectively : median OSDI 16 (IQR 6–39) and 12.5 (IQR 8–39) (p = 0.380); mean NIBUT 10.30 (SD ± 2.62) and 10.78 (SD ± 2.92) ( s, p = 0.476); median blinking quality 100 (IQR 100) and 100 (IQR 100 ) (%, p = 0.188); median lipid layer 87 (IQR 77–90) and 86 (IQR 74–100) (nm, p = 0.451); median meniscus height 0.22 (IQR 0.19-0,31) and 0.24 (IQR 0.20–0.27) (mm, p = 0.862), median Meibomian gland atrophy 33 (IQR 24–45) and 31.5 (IQR 25–39) (%, p = 0.524); and mean osmolarity 306.6 (SD ± 21.13) and 313.8 (SD ± 29) (mOsm, p = 0.297). There was no statistically significant relationship between the repetitive use of 2% iodinated solution and signs or symptoms compatible with dry eye syndrome in this group of patients. Conclusions The findings suggest that 2% povidone iodine is a safe and efficacious agent for ocular surface antisepsis during intravitreal injections, not leading to substantial ocular surface modifications. This conclusion supports the continued use of povidone iodine in routine ophthalmic procedures without increased risk of inducing dry eye syndrome.

Natalia A Warren,1,2,&ast; Steven L Maskin,3,&ast; Varadraj Gurupur,4,&ast; Deidre A Rector,1,&ast; Diana Adelman,1,&ast; Susan Howell,1,&ast; John McAree,1,&ast; Ruthie Dibble,1,&ast; Celia Carlisano,1,&ast; David P Maconi,1,&ast; Dirk Schrotenboer,5,&ast; Maria Jaimes,3,&ast; Nancy Marte,3,&ast; Theresa Carlisano,1,&ast; Claire Toland,3,&ast; Jongik Chung,6,&ast; Sandra L Cremers,7 Glenn S Corbin8 1Not A Dry Eye Foundation, Daytona Beach, FL, USA; 2School of Modeling, Simulation, and Training, University of Central Florida, Orlando, FL, USA; 3Dry Eye and Cornea Treatment Center, Tampa, FL, USA; 4Department of Health Management and Informatics, University of Central Florida, Orlando, FL, USA; 5Dry Eye Spa of West Michigan, Holland, MI, USA; 6Department of Statistics and Data Science, University of Central Florida, Orlando, FL, USA; 7Johns Hopkins Medical Institution, Baltimore, MD, USA; 8Wyomissing Optometric Center, Inc, Wyomissing, PA, USA&ast;These authors contributed equally to this workCorrespondence: Natalia A Warren, Not A Dry Eye Foundation, 1019 Sea Shell Court, Daytona Beach, FL, 32124, Tel +1 855-544-6553, Email Natalia.warren@notadryeye.orgIntroduction: Although affecting an estimated 35% of the population, Dry Eye is not well understood by patients and the medical community. As a result, both in research and clinical settings, diagnostic and treatment protocols tend to be non-specific, ad hoc, and inadequate, with a narrow industry-driven focus. The purpose of this convening was to propose a research roadmap that orients Dry Eye researchers toward a comprehensive patient-centered approach to diagnosing and treating Dry Eye, Meibomian gland dysfunction (MGD), and related comorbidities with a goal of improving clinical outcomes for Dry Eye/MGD patients.Methods: Sixteen participants, including Dry Eye/MGD patients, caregivers, and patient advocates together with a group of experts in Dry Eye, MGD and other fields identified gaps in research on Dry Eye and MGD diagnostic and treatment approaches (age range 20– 80; male to female ratio of 7:11; patients: 7). During a 2-day virtual convening, participants were assigned to topic-specific focus-group sessions to discuss and develop research questions pertaining to Dry Eye and MGD. The research questions were compiled into a proposed patient-centered roadmap for Dry Eye and MGD research. Two additional participants contributed to the proposed roadmap following the convening.Results: The focus groups identified over 80 patient-centered research questions important to patients and other stakeholders and compiled these into a proposed research roadmap.Conclusion: The convened stakeholders aim to establish a cohesive and comprehensive patient-centered approach to treating Dry Eye, Meibomian Gland Dysfunction, and comorbidities. The research roadmap will serve as a reference for researchers, educational institutions, clinicians, and others evaluating diagnostic and treatment protocols in Dry Eye and MGD.Keywords: dry eye disease, Meibomian gland dysfunction, patient-centered research, patient advocacy, ocular surface disease, patient care

Objectives: Ocular surface reactions (OSR) have been associated with dupilumab for atopic dermatitis (AD) treatment. However, the association of dupilumab‐associated OSR (DA‐OSR) for nasal polyps (CRSwNP) treatment has not been studied. We evaluated DA‐OSR for CRSwNP treatment using the FDA Adverse Event Reporting System (FAERS). Methods: FAERS was queried for any general ocular reactions (DA‐GOR) from 2019Q1 to 2022Q4. DA‐OSR were subcategorized from DA‐GOR and compared between treatment groups (CRSwNP, asthma, AD). Logistic regression was used to predict DA‐OSR. Disproportionality analysis (DPA) of DA‐OSR was performed using OpenVigil. Results: There were 60,198 total observations, of which 5344 were treated for CRSwNP. The prevalence of DA‐GOR and DA‐OSR was greatest for AD (15.3%, 7.8%), followed by CRSwNP (12.2%, 6.7%) and asthma (9.2%, 3.5%). The most commonly reported OSRs were dry eyes (35.9%), conjunctivitis (15.7%), and increased lacrimation (11.0%). The reported odds ratio (ROR) of CRSwNP‐treated DA‐OSR was 0.84 (0.73–0.97; p = 0.015), compared to 1.29 (1.20–1.40; p < 0.001) for AD and 0.66 (0.59–0.73; p < 0.001) for asthma. For CRSwNP treatment, the DA‐OSR ROR was 0.97 (0.90–1.03; p = 0.3) for men and 0.78 (0.73–0.83, p < 0.001) for older adults (age > 50). ROR in the DPA for DA‐OSR was 12.5 (12.2–12.8; p < 0.001) for any indication and 0.58 (0.53–0.64; p < 0.001) for CRSwNP treatment only. Conclusions: While there are limitations to FAERS, this study confirms the association between dupilumab and OSR for AD treatment, and does not support an association between dupilumab and OSR for CRSwNP treatment. Younger adults experience more DA‐OSR in CRSwNP treatment without a specific predilection for sex. Level of Evidence: IV Laryngoscope, 134:2602–2608, 2024 [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic metabolic disorder marked by hyperglycemia due to defects in insulin secretion, action, or both, with a global prevalence that has tripled in recent decades. This condition poses significant public health challenges, affecting individuals, healthcare systems, and economies worldwide. Among its numerous complications, ocular surface disease (OSD) is a significant concern, yet understanding its pathophysiology, diagnosis, and management remains challenging. This review aims to explore the epidemiology, pathophysiology, clinical manifestations, diagnostic approaches, and management strategies of diabetes-related OSD. The ocular surface, including the cornea, conjunctiva, and associated structures, is vital for maintaining eye health, with the lacrimal functional unit (LFU) playing a crucial role in tear film regulation. In DM, changes in glycosaminoglycan metabolism, collagen synthesis, oxygen consumption, and LFU dysfunction contribute to ocular complications. Persistent hyperglycemia leads to the expression of cytokines, chemokines, and cell adhesion molecules, resulting in neuropathy, tear film abnormalities, and epithelial lesions. Recent advances in molecular research and therapeutic modalities, such as gene and stem cell therapies, show promise for managing diabetic ocular complications. Future research should focus on pathogenetically oriented therapies for diabetic neuropathy and keratopathy, transitioning from animal models to clinical trials to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Background: The use of povidone-iodine for ocular surface asepsis is widespread for intravitreal injections. They became frequent procedures, leading to serial exposure of patients' eyes to iodinated solutions. In this study, we investigate the changes in the ocular surface in patients submitted to repeated use of povidine for intravitreal injection of anti-VEGF asepsis, analyzing Ocular Surface Disease Index, non-invasive break up time, blinking quality, lipid layer, meniscus height and osmolarity. Methods: This case-control study included 34 individuals (68 eyes), 14 males, 20 females aged 48 to 94. Inclusion criteria were individuals who received application of 2% povidone-iodine eyedrops for intravitreal injections treatment with the non-treated contralateral eye used as control. Ocular surface examinations were performed at a single occasion. A pre-intravitreal injection asepsis protocol with povidone-iodine was applied. All statistical analysis was performed using the STATA® 18.0 Software and a p-value = 0.05 was considered as the statistical significance value in all tests. Results: The median number of IVIs in treated eyes was 12 (range 6–20). The results in treated eyes compared with untreated eyes were respectively : median OSDI 16 (IQR 6–39) and 12.5 (IQR 8–39) (p = 0.380); mean NIBUT 10.30 (SD ± 2.62) and 10.78 (SD ± 2.92) (s, p = 0.476); median blinking quality 100 (IQR 100) and 100 (IQR 100) (%, p = 0.188); median lipid layer 87 (IQR 77–90) and 86 (IQR 74–100) (nm, p = 0.451); median meniscus height 0.22 (IQR 0.19-0,31) and 0.24 (IQR 0.20–0.27) (mm, p = 0.862), median Meibomian gland atrophy 33 (IQR 24–45) and 31.5 (IQR 25–39) (%, p = 0.524); and mean osmolarity 306.6 (SD ± 21.13) and 313.8 (SD ± 29) (mOsm, p = 0.297). There was no statistically significant relationship between the repetitive use of 2% iodinated solution and signs or symptoms compatible with dry eye syndrome in this group of patients. Conclusions: The findings suggest that 2% povidone iodine is a safe and efficacious agent for ocular surface antisepsis during intravitreal injections, not leading to substantial ocular surface modifications. This conclusion supports the continued use of povidone iodine in routine ophthalmic procedures without increased risk of inducing dry eye syndrome. [ABSTRACT FROM AUTHOR]

Background: Insulin and insulin-like growth factor (IGF)-1 receptors are present in ocular tissues such as corneal epithelium, keratocytes, and conjunctival cells. Insulin plays a crucial role in the growth, differentiation, and proliferation of corneal epithelial cells, as well as in wound healing processes in various tissues. Purpose: This review explores the potential role of topical insulin in the treatment of ocular surface diseases. Specifically, it examines its impact on corneal nerve regeneration, sub-basal plexus corneal nerves, and its application in conditions like corneal epithelial defects, dry eye disease, and diabetic keratopathy. Methods: The review analyzes studies conducted over the past decade that have investigated the use of topical insulin in ocular surface diseases. It focuses on indications, drug preparation methods, side effects, efficacy outcomes, and variations in insulin concentrations and dosages used. Results: While off-label use of topical insulin has shown promising results in refractory corneal epithelial defects, its efficacy in dry eye disease is yet to be demonstrated. Variations in concentrations, dilutions, and dosing guidelines have been reported. However, limited data on ocular penetration, ocular toxicity, and systemic side effects pose challenges to its widespread utility. Conclusion: This review synthesizes findings from ocular investigations on topical insulin to assess its potential applicability in treating ocular surface and corneal diseases. By highlighting indications, preparation methods, side effects, and efficacy outcomes, it aims to provide insights into the current status and future prospects of using topical insulin in ophthalmic practice. [ABSTRACT FROM AUTHOR]

To benchmark the epidemiologic features of pediatric ocular surface inflammatory diseases (POSID). Retrospective cohort study. Patients 18 years of age or younger with a medical claim for a diagnosis of POSID in the Optum Labs Data Warehouse between 2007 and 2020. Patients with claims of blepharokeratoconjunctivitis (BKC), herpes simplex keratoconjunctivitis (HSK), or vernal keratoconjunctivitis (VKC) were included. Those with less than 6 months of follow-up before the initial diagnosis of POSID were excluded. Odds ratios (ORs) were derived from multivariable logistic regression analyses evaluating the associations between epidemiologic variables and POSID development. The primary outcome was the estimated prevalence of POSID. Prevalence of POSID subtypes and changes in prevalence over time were also evaluated. Two thousand one hundred sixty-eight patients with POSID were identified from 2018 through 2019, yielding an estimated prevalence of 3.32 per 10 000. The prevalence of POSID was higher among children between 5 and 10 years of age, male children, those of Asian descent, and those living in the Northeast and the West census regions of the United States. The prevalence (per 10 000) of BKC, HSK, and VKC in the same period were 0.59 (95% confidence interval [CI], 0.53–0.65), 0.74 (95% CI, 0.68–0.81), and 1.99 (95% CI, 1.88–2.10), respectively, and significant differences were found in terms of age, sex, racial, ethnic, and regional distributions among the diagnoses. Between 2008 through 2009 and 2018 through 2019, a significant increase in POSID was noted among Asians (from 6.26 [95% CI, 5.28–7.36] to 11.80 [95% CI, 10.40–13.34]) driven by changes in VKC. Multivariable analysis demonstrated that age older than 5 years (OR, 2.57–3.75; 95% CI, 2.17–4.34), male sex (OR, 1.38; 95% CI, 1.26–1.50), Asian descent (OR, 3.12; 95% CI, 2.70–3.60), and Black or African American descent (OR, 1.26; 95% CI, 1.02–1.55) were associated with POSID development. This study provides an estimated prevalence of POSID and its 3 common subtypes in the United States, with important epidemiologic differences among them. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (= 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (= 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 (n = 28), 0.10 ± 0.32 (n = 10), 0.19 ± 0.40 (n = 16). The NIBUT groups were significantly correlated with COS (p-value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 (p-value = 0.041) and between Groups 1 and 3 (p-value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS. [ABSTRACT FROM AUTHOR]

Background: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab‐associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. Methods: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non‐AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. Results: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL‐12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non‐AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. Conclusions: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD. [ABSTRACT FROM AUTHOR]

Copyright of MN Opthalmology / MN Oftalmoloji is the property of Medical Network and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Purpose: This case report highlights a possible association between netarsudil use and crystalline keratopathy. Observations: Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment. Conclusions and importance: Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.

Costanza Rossi,1,&ast; Sabrina Vaccaro,1,&ast; Massimiliano Borselli,1 Giovanna Carnovale Scalzo,1 Mario Damiano Toro,2 Vincenzo Scorcia,1 Giuseppe Giannaccare3 1Department of Ophthalmology, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Eye Clinic, Public Health Department, University of Naples Federico II, Naples, Italy; 3Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy&ast;These authors contributed equally to this workCorrespondence: Giuseppe Giannaccare, Ophthalmology, Chairman of Eye Clinic, Department of Surgical Sciences, University of Cagliari, Cagliari, Italy, Email giuseppe.giannaccare@unica.itPurpose: To report the outcomes of a novel microwave heating device (Blepha EyeBag®) used serially for the treatment of meibomian gland dysfunction (MGD).Patients and Methods: This prospective single center study was conducted at University Magna Graecia of Catanzaro. Patients were instructed to apply the compress twice daily for 15 days and once per day every two days, as reported in the package insert. Outcome measures were i) ocular surface disease index (OSDI) score, ii) tear meniscus height (TMH), iii) non-invasive keratograph break-up time (NIKBUT) (first and average), iv) meiboscore, v) bulbar redness. Evaluations were performed at baseline (T0) after 15 days (T1) and after 45 days of therapy (T2).Results: Overall, 19 patients with MGD (8 males, 11 females; mean age 64.58 ± 9.72 years) were included. The mean value of OSDI score showed a significant decrease from 28.16 ± 17.46 at T0 to 13.69 ± 7.62 at T2 (p=0.008). The mean value of NIKBUT first significantly increased from 6.67 ± 3.51 seconds (s) at T0 to 10.46 ± 4.64 at T2 (p=0.0121); in parallel, the mean value of NIKBUT average increased significantly from 11.09 ± 4.15 s at T0 to 14.95 ± 4.85 at T2 (p=0.0049). No significant differences were detected at each time point for bulbar redness, meiboscore and TMH. Throughout the entire study, no adverse events were recorded.Conclusion: The microwave-heated eye bag treatment is both safe and effective for treatment of MGD, being able to significantly ameliorate both patient-reported symptoms and tear film stability.Keywords: MGD, dry eye, ocular surface disease, warming device, eyelid

Purpose: To examine the ocular surface disease in primary open-angle glaucoma (POAG) patients already on treatment versus POAG patients without treatment. Methods: A prospective cohort study was conducted on 120 eyes of 60 POAG patients: 60 treatment-naïve eyes (group I) and 60 eyes already on topical anti-glaucoma medications (AGMs) (group II). All patients had filled out the Ocular Surface Disease Index (OSDI) questionnaire and underwent a comprehensive glaucoma workup. Tear break-up time (TBUT) test, Schirmer's test (type I), corneal sensitivity, anterior segment-optical coherence tomography (AS-OCT), and corneal and conjunctival staining were done at day 1, 1 month, 3 months, 6 months, and 12 months follow-up. Results: On presentation, TBUT, Schirmer's test, tear meniscus height (TMH), and tear meniscus depth (TMD) were significantly higher in group I compared to group II. No significant difference was noted in OSDI score, corneal sensitivity, and tear meniscus area (TMA) between the groups on presentation. Both, lissamine green and rose bengal staining, had higher grades in group II compared to group I. Worsening of ocular surface disease was noted in both groups on follow-up. OSDI score, TBUT, Schirmer's test, TMH, and TMD had better values in group I in comparison to group II on follow-up. Conclusion: The study has identified glaucoma patients on AGMs to be more affected by dry eye disease (DED) compared to treatment-naive glaucoma patients. We found statistically significant differences in values of TBUT, Schirmer tests, lissamine and rose bengal staining, and AS-OCT parameters at baseline and 3, 6, and 12 months follow-up. OSDI scores showed significant differences at 6 and 12 months of follow-up. We recommend consideration of evaluation and management of DED/ocular surface disease in glaucoma patients on topical AGMs, particularly multiple drugs and doses.

Purpose: Inhibitors of dihydroorotate dehydrogenase (DHODH) have been found to be potent anti-inflammatory agents. Recently, a topical formulation (KIO-101 eye drops) of a DHODH inhibitor has been developed. The aim of the present study was to evaluate the safety and tolerability of KIO-101 eye drops in Healthy Volunteers (HVs) and patients with conjunctival hyperemia. Methods: The study was carried out in a double-masked, placebo-controlled, randomized, parallel-group design with two parts. In part I, HVs received single and multiple instillations (four times daily for 12 consecutive days) of KIO-101 eye drops in ascending doses of 0.05%, 0.15%, and 0.30%, respectively. Part II was conducted in patients with conjunctival hyperemia who received 0.15% KIO-101 eye drops twice daily for 12 consecutive days. Ophthalmic and systemic safety examinations were performed on all participants. In part II, ocular hyperemia grading and an ocular surface disease index (OSDI) questionnaire were performed. Results: 24 HVs participated in part I and 21 patients in part II. KIO-101 eye drops were well tolerated in all subjects. No serious adverse events (SAEs) occurred, and all AEs that were reported were transient and considered mild to moderate. In the highest dose cohort (0.30%), epistaxis occurred in two subjects after multiple instillations. In part II, after 12 days treatment with 0.15% KIO-101, conjunctival hyperemia decreased by −1.1 ± 0.27 points in the treatment and −0.6 ± 0.79 points in the placebo group (p = 0.0385). OSDI decreased from 47.9 ± 18.7 to 27.6 ± 19.13 points in the treatment group, while in the placebo group, a change from 41.3 ± 12.08 to 27.3 ± 18.63 points occurred. Conclusions: A 12-day treatment regimen with topical KIO-101 eye drops at low and mid doses was safe and well tolerated in both HVs and patients with conjunctival hyperemia. The obtained results point towards an early sign of reduction in conjunctival hyperemia. [ABSTRACT FROM AUTHOR]

Purpose: To examine the ocular surface disease in primary open-angle glaucoma (POAG) patients already on treatment versus POAG patients without treatment. Methods: A prospective cohort study was conducted on 120 eyes of 60 POAG patients: 60 treatment-naïve eyes (group I) and 60 eyes already on topical anti-glaucoma medications (AGMs) (group II). All patients had filled out the Ocular Surface Disease Index (OSDI) questionnaire and underwent a comprehensive glaucoma workup. Tear break-up time (TBUT) test, Schirmer's test (type I), corneal sensitivity, anterior segment-optical coherence tomography (AS-OCT), and corneal and conjunctival staining were done at day 1, 1 month, 3 months, 6 months, and 12 months follow-up. Results: On presentation, TBUT, Schirmer's test, tear meniscus height (TMH), and tear meniscus depth (TMD) were significantly higher in group I compared to group II. No significant difference was noted in OSDI score, corneal sensitivity, and tear meniscus area (TMA) between the groups on presentation. Both, lissamine green and rose bengal staining, had higher grades in group II compared to group I. Worsening of ocular surface disease was noted in both groups on follow-up. OSDI score, TBUT, Schirmer's test, TMH, and TMD had better values in group I in comparison to group II on follow-up. Conclusion: The study has identified glaucoma patients on AGMs to be more affected by dry eye disease (DED) compared to treatment-naive glaucoma patients. We found statistically significant differences in values of TBUT, Schirmer tests, lissamine and rose bengal staining, and AS-OCT parameters at baseline and 3, 6, and 12 months follow-up. OSDI scores showed significant differences at 6 and 12 months of follow-up. We recommend consideration of evaluation and management of DED/ocular surface disease in glaucoma patients on topical AGMs, particularly multiple drugs and doses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present paper was to investigate the impact of lacrimal gland reposition procedure on ocular surface parameters, and the paper seeks to fill a gap about a subject that has not been studied in detail before. Materials and Methods: The medical records of patients who underwent upper eyelid blepharoplasty surgery along with lacrimal gland repositioning procedure (Group 1) and patients who underwent only upper eyelid blepharoplasty (Group 2) between October 2021 and March 2023 were retrospectively analyzed. Postoperative final visit tear break-up time (TBUT), tear meniscus height (TMH), Schirmer's test and ocular surface disease index (OSDI) questionnaire was compared with preoperative values separately in each group. Additionally, these tests were compared between the two groups. Results: The postoperative OSDI score was significantly higher (p: 0.04), and the postoperative TMH was significantly lower (p: 0.03) in lacrimal gland surgery group when compared with standard blepharoplasty group. Additionally, in lacrimal gland surgery group, the postoperative TMH was significantly lower and OSDI scores were significantly higher when compared with the preoperative values (p: 0.03 for TMH and p: 0.03 for OSDI score). Conclusion: Reposition of a prolapsed lacrimal gland can result with ocular surface disease. In those cases, the physicians should be aware of this potential complication before surgery planning and take appropriate measures to minimize the risks. [ABSTRACT FROM AUTHOR]

We aim to summarize the current evidence of Vascular endothelial growth factors (VEGF)s in external eye diseases and determine whether serum and plasma VEGF levels are associated with tear and ocular surface tissues. A systematic search of PUBMED and EMBASE was conducted using PRISMA guidelines between October 2022 and November 2023, with no restriction on language or publication date. Search terms included relevant MESH terms. These studies were evaluated for quality, and an assessment of the risk of bias was also carried out. Extracted data were then visually represented through relevant tables or figures. The initial literature search yielded 777 studies from PUBMED, 944 studies from EMBASE, and 10 studies from manual searches. Fourteen eligible studies were identified from 289 articles published from 2000 to 2023 in the English language or with English translations, including rabbit models, murine models, and human-derived samples. Most studies were retrospective in nature and case–control studies. Various common external eye diseases, such as dry eye disease (DED) and allergic eye disease were investigated. Despite limitations and small sample sizes, researchers have found elevated tissue levels of the VEGF in the vascularized cornea, especially in animal models, but there is no evidence of clear changes in the tear concentrations of VEGF in DED and allergic eye disease. Tear VEGF is associated with corneal vascularization. Anti-VEGF therapies may have the potential to manage such conditions. [ABSTRACT FROM AUTHOR]

Background: Corneal perforation is an ophthalmic emergency. The conventional management of corneal perforation can be associated with severe complications especially in patients with ocular surface disease. Endothelial keratoplasty has been suggested as an alternative surgical technique for the management of corneal perforations. We present a case series of nine patients with corneal perforation and ocular surface disease managed with secondary patch endothelial keratoplasty. Methods: This is a retrospective case series of nine patch endothelial keratoplasties performed between 2016 and 2022 at a quaternary eye hospital in Australia. The surgical technique is similar to conventional endothelial keratoplasty except descemetorhexis was not performed. Results: A total of 9 cases were treated during the review period. Eight of the nine cases had an improvement in visual acuity. One case failed to achieve corneal tectonic objective. Conclusion: Patch endothelial keratoplasty is a safe secondary procedure for the management of corneal perforations in patients with ocular surface disease. [ABSTRACT FROM AUTHOR]

Copyright of Spektrum der Augenheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sjögren's syndrome dry eye (SSDE) is a subset of Sjögren's syndrome marked by dry eye symptoms that is distinct from non-Sjögren's syndrome dry eye (NSSDE). As SSDE can lead to severe complications, its early detection is imperative. However, the differentiation between SSDE and NSSDE remains challenging due to overlapping clinical manifestations. This review endeavors to give a concise overview of the classification, pathophysiology, clinical features and presentation, ocular and systemic complications, clinical diagnosis, and management of SSDE. Despite advancements, limitations in current diagnostic methods underscore the need for novel diagnostic modalities. Thus, the current review examines various diagnostic biomarkers utilized for SSDE identification, encompassing serum, salivary, and tear analyses. Recent advancements in proteomic research and exosomal biomarkers offer promising diagnostic potential. Through a comprehensive literature review spanning from 2016 to 2023, we highlight molecular insights and advanced diagnostic modalities that have the potential to enhance our understanding and diagnosis of SSDE. [ABSTRACT FROM AUTHOR]