A case of IgG4-related ophthalmic disease after SARS-CoV-2 vaccination: case report and literature review.

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is affecting the world with a surge in cases. A variety of autoimmune diseases occur after SARS-CoV-2 infection or vaccination, of which IgG4-related disease (IgG4-RD) is an important type. IgG4-RD can involve multiple organs of the body. The ocular manifestation of IgG4-RD is called IgG4-related ophthalmic disease (IgG4-ROD). We herein report a patient diagnosed with IgG4-ROD. The patient developed ptosis and vision loss after SARS-CoV-2 vaccination, and the symptoms worsened after SARS-CoV-2 infection. After excluding other diseases like myasthenia gravis and Eaton-Lambert syndrome that may cause ptosis, the diagnosis of IgG4-ROD was confirmed by pathological examination. We discussed the predisposing factors, diagnosis and treatment of this patient to provide a more empirical and theoretical basis for clinical diagnosis and treatment. We conducted a literature review of previously reported cases of IgG4-RD following SARS-CoV-2 infection or vaccination. We retrieved a total of 9 cases, of which 5 developed symptoms after vaccination and 4 after infection. Demographic and clinical characteristics were summarized. In conclusion, our case represents the first case of proven IgG4-ROD after COVID-19 vaccination. We believe that IgG4-ROD and SARS-CoV-2 infection or vaccination are closely related, and the immune system disorder caused by SARS-CoV-2 infection or vaccination may be a key factor in the pathogenesis of IgG4-RD. But for now, there is no direct evidence that there is a causal relationship between SARS-CoV-2 infection or vaccination and IgG4-ROD, which still needs more research and exploration to confirm.

Air Pollution and Chronic Eye Disease in Adults: A Scoping Review.

PURPOSE: We conducted a scoping review of studies examining ambient air pollution as a risk factor for chronic eye disease influencing the lens, retina, and intraocular pressure in adults. METHODS: Terms related to air pollution and eye disease outcomes were used to search for publications on Embase, Web of Science Core Collection, Global Health, PubMed, and the Cochrane Central Register of Controlled Trials from January 1, 2010, through April 11, 2022. RESULTS: We identified 27 articles, focusing on the following non-mutually exclusive outcomes: cataract (n = 9), presbyopia (n = 1), retinal vein occlusion or central retinal arteriolar and venular equivalents (n = 5), intraocular pressure (IOP) (n = 3), glaucoma (n = 5), age-related macular degeneration (AMD) (n = 5), diabetic retinopathy (n = 2), and measures of retinal morphology (n = 3). Study designs included cross-sectional (n = 16), case-control (n = 4), and longitudinal (n = 7). Air pollutants were measured in 50% and 95% of the studies on lens and retina or IOP, respectively, and these exposures were assigned to geographic locations. Most research was conducted in global regions with high exposure to air pollution. Consistent associations suggested a possibly increased risk of cataract and retina-associated chronic eye disease with increasing exposure to particulate matter (PM2.5-PM10), NO2, NOx, and SO2. Associations with O3 were less consistent. CONCLUSIONS: Accumulating research suggests air pollution may be a modifiable risk factor for chronic eye diseases of the lens and retina. The number of studies on each specific lens- or retina-related outcome is limited. Guidelines regarding the role of air pollution in chronic eye disease do not exist.

Ocular toxicities of fibroblast growth factor receptor inhibitors: A review.

Fibroblast growth factor receptor (FGFR) inhibitors are an emerging class of small molecule targeted cancer drugs with promising therapeutic possibilities for a wide variety of malignancies. While ocular adverse events from FGFR inhibitors are reported in clinical trials, subsequent case studies continue to reveal new toxicities. Disease pathology affecting multiple parts of the eye has been reported, but the ocular surface and the retina are the most commonly encountered areas affected by FGFR inhibitors, manifesting as dry eye and FGFR inhibitor-associated retinopathy, respectively. Corneal thinning and melt is a rare but serious and potentially vision-threatening complication of FGFR inhibitor toxicity. Similarities between toxicities observed from other targeted cancer therapy drugs and FGFR inhibitors may help us understand underlying pathophysiological changes. The management of these adverse events requires close ophthalmologic follow-up and may require discontinuation of the offending agents in some cases.

Association between air pollution and emergency room admission for eye diseases in Rome, Italy: A time-series analysis.

Eye diseases impose a significant burden on health services due to high case numbers. However, exposure to outdoor air pollution is seldom mentioned as potential harmful factor. We conducted a time-series analysis in Rome, Italy, to estimate the association between daily mean concentration of NO2, PM10 and PM2.5 and daily number of emergency room (ER) admissions for a selected cluster of eye diseases from 2006 to 2016. We used Poisson regression adjusted for time trend, population decrease during summer vacations and holidays, day of week, apparent temperature (hot and cold) and daily concentration of nine pollen species. We observed 581,868 ER admissions during the study period. 44.74% of cases were observed in subjects with less than 20 years, 19.50% in 51-65 age category and 13.4% among children (0-14 years). No differences between sexes were recorded. Mean values of pollutant concentrations were 54.75, 31.01 and 18.14 µg/m3 for NO2, PM10 and PM2.5 respectively. The air temperature ranged from -1 °C to 32.5 °C, with a mean value of 16 °C (SD = 6.88). The apparent temperature spaced from -3.58 °C to 34.08 °C (mean = 15.61 °C, SD = 8.5). The highest percent risk increases for 10 µg/m3 increases of the three pollutants were observed at lag0-1 day (1.3%, 0.63-1.98 for PM2.5; 1.03%, 0.56-1.51 for PM10 and 0.6%, 0.13-1.07 for NO2). Risk increased significantly also at lag0 and lag0-5 day for each pollutant. Secondary analyses showed higher effects in the elderly compared to younger subjects. No differences emerged between sexes. The dose response analysis suggested of possible effects on ER admission risk also at low-level concentrations of PM2.5. A strong confounding effect of pollen was not detected. RESULTS: of this study are coherent with previous analyses. Speculation can be done about the biological mechanisms that link air pollution to eye damage.

Environmental exposures to cadmium and lead as potential causes of eye diseases.

Humans are exposed to cadmium and lead in various regions of the world daily due to industrial development and climate change. Increasing numbers of preclinical and clinical studies indicate that heavy metals, such as cadmium and lead, play a role in the pathogenesis of eye diseases. Excessive exposure to heavy metals such as cadmium and lead can increase the risk of impaired vision. Therefore, it is essential to better characterize the role of these non-essential metals in disease etiology and progression. This article discusses the potential role of cadmium and lead in the development of age-related eye diseases, including age-related macular degeneration, cataracts, and glaucoma. Furthermore, we discuss how cadmium and lead affect ocular cells and provide an overview of putative pathological mechanisms associated with their propensity to damage the eye.

Presumed Silicone Oil Droplets After Intravitreal Pegcetacoplan Injections.

Importance: Recently, intravitreal pegcetacoplan became the first drug to gain US Food and Drug Administration approval for the treatment of geographic atrophy associated with nonexudative age-related macular degeneration, but the administration of this medication may be associated with unanticipated posttreatment complications. Objective: To assess the prevalence of presumed silicone oil droplets in the vitreous cavity after intravitreal injection of pegcetacoplan. Design, Setting, and Participants: This case series study involved a retrospective record review of all 55 patients treated with intravitreal pegcetacoplan, 0.1 mL in 150-mg/mL solution, between March 24 and June 5, 2023, at a single specialty retina practice. All injections were done using needles from the kit supplied by Apellis Pharmaceuticals on a 1-mL McKesson Luer lock syringe. Main Outcomes and Measures: The presence or absence of presumed silicone bubbles detected during dilated biomicroscopic fundus examination and/or on color fundus photographs, the presence or absence of symptoms, change in visual acuity, and/or increase in intraocular pressure. Results: A total of 62 intravitreal pegcetacoplan injections were given to 55 patients (mean [SD] age, 83.8 [7.8] years; 33 women [60%]) from March 24 to June 5, 2023. Of the 55 patients, 16 (29%; mean [SD] age, 83.8 [7.4] years; 9 women [56%]) had presumed intravitreal silicone droplets discovered 2 to 4 weeks after treatment, 3 of which were documented on color fundus photographs. Of the 16 patients, 14 (88%) were symptomatic for new floaters that they described as persistent, while 2 (13%) were asymptomatic. There were no signs of inflammation or infection, no increases in intraocular pressure, and no changes in visual acuity for all 16 patients. Conclusions and Relevance: A substantial percentage of patients had symptomatic floaters from presumed intravitreal silicone oil droplets after injections of pegcetacoplan using a McKesson 1-mL Luer lock syringe. These findings support consideration of informing patients of this potential adverse effect, avoiding use of the McKesson syringe, and considering use of silicone-free syringes for pegcetacoplan injections.

The effect of baseline intraocular pressure and anterior segment parameters on intraocular pressure after intravitreal bevacizumab injection.

PURPOSE: We aimed to compare the predictive effect of pre-injection intraocular pressure (IOP) and anterior segment parameters on post-injection IOP values after intravitreal bevacizumab injection for neovascular age-related macular degeneration (NVAMD) in phakic and pseudophakic patient groups. MATERIAL AND METHODS: This retrospective cross-sectional study included 65 eyes of 65 treatment-naive NVAMD patients. Patients were divided into two groups according to their lens status (35 phakic and 30 pseudophakic patients). Pre-injection IOP, anterior segment parameters measured with PENTACAM, and post-injection IOP values measured at the 5th minute were recorded. Univariate and multivariate regression analyses were used to recognise the predictive effect of pre-injection IOP and anterior segment parameters on post-injection IOP for each group. RESULTS: Multivariate regression analyses showed that the decrease in anterior chamber depth (ACD), and the increase in pre-injection IOP were significantly correlated with higher post-injection IOP in the phakic patient group (p = 0.019 and 0.031; respectively). No correlation was found in the pseudophakic patient group. CONCLUSION: Pre-injection ACD and IOP values may be predictive of higher post-injection IOP in phakic patients. Preoperative assessment of these parameters could be beneficial in patients at risk of glaucoma.

Cardiovascular and Cerebrovascular Safety of Ranibizumab, Bevacizumab, and Aflibercept in Ocular Diseases: An Analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

The cardiovascular and cerebrovascular safety of ranibizumab, bevacizumab, and aflibercept for ocular diseases is unclear. This study aimed to evaluate and compare the cardiovascular and cerebrovascular safety in patients receiving ranibizumab, bevacizumab, and aflibercept for ocular disease. A cross-sectional study was conducted from 2017 (Q1) to 2021 (Q4) in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. The outcomes of interest were central nervous system vascular disorders, ischemic heart disease, hypertension, pulmonary hypertension, torsade de pointes/QT prolongation, embolic and thrombotic events, cardiac arrhythmias, cardiac failure, and cardiomyopathy. Data mining was performed by a disproportional method with a compression, using compressed reporting odds ratios (sRORs) with 95% confidence intervals (CIs) to measure signals. The results showed 1462 cardiovascular and cerebrovascular events associated with aflibercept, 834 with ranibizumab, and 150 with bevacizumab. Ranibizumab, bevacizumab, and aflibercept were linked to central nervous system vascular disorders (sROR, 5.57[95%CI, 4.95-6.26] vs sROR, 2.23 [95%CI, 1.75-2.85] vs sROR, 2.73[95%CI, 2.43-3.06]), ischemic heart disease (sROR, 3.31[95%CI, 2.65-4.13] vs sROR, 1.98 [95%CI, 1.24-3.16] vs sROR, 3.00 [95%CI, 2.46-3.65]), embolic and thrombotic (sROR, 3.36 [95%CI, 3.04-3.72] vs sROR, 2.16 [95%CI, 1.70-2.74] vs sROR, 5.25 [95%CI, 4.82-5.72]). Both ranibizumab and bevacizumab produced hypertension (sROR, 1.73 [95%CI, 1.41-2.12] vs sROR, 1.46 [95%CI, 1.03-2.06]) and arrhythmias (sROR, 2.82 [95%CI, 1.99-3.99] vs sROR, 2.13 [95%CI, 1.08-4.22]) signals. The signals of heart failure were detected in ranibizumab (sROR, 5.64 [95%CI, 4.08-7.79]) and aflibercept (sROR, 2.80 [95%CI, 2.03-3.86]). Ranibizumab, bevacizumab, and aflibercept for ocular disease have different safety profiles in cardiovascular and cerebrovascular. The overall cardiovascular and cerebrovascular risk of the patient should be thoroughly assessed in order to select the safest drug for treatment.

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis.

AIMS: To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We conducted a disproportionality analysis of PCSK9 inhibitors in the FAERS (01/2004-12/2021). The association between PCSK9 inhibitors and oAEs was evaluated using the information component (IC) and the reporting odds ratio (ROR), and the difference in oAEs between evolocumab and alirocumab was compared using the ROR. Different sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: A total of 103 531 reports involving at least 1 PCSK9 inhibitor were found in the FAERS. PCSK9 inhibitors were associated with higher reporting of increased lacrimation (IC 0.27 [95% confidence interval {CI} 0.02-0.45]; ROR 1.21 [95% CI 1.04-1.40]), seasonal allergy (IC 0.39 [95% CI 0.04-0.64]; ROR 1.32 [95% CI 1.07-1.62]) and eye operation (IC 0.66 [95% CI 0.04-1.10]; ROR 1.60 [95% CI 1.11-2.30]) compared with the full database, and there was no difference between evolocumab and alirocumab. Sensitivity analyses showed that the disproportionate signals of increased lacrimation disappeared after excluding cases with other lipid-lowering agents in the combined drugs. Except for eye operations, most of these adverse events occurred within 30 days of the first dose, and all 3 oAEs were mostly reported in women and individuals >65 years. CONCLUSION: This pharmacovigilance study identified a possible signal of ocular disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations in PCSK9 inhibitors medication.

Dupilumab-associated ocular surface disease: An interdisciplinary decision framework for prescribers in the Australian setting.

BACKGROUND/OBJECTIVES: Dupilumab-associated ocular surface disease (DAOSD) is of particular relevance in patients with atopic dermatitis (AD). Guidance on DAOSD assessment and management in the Australian setting is needed to reduce its impact and minimise disruption to treatment. METHODS: A systematic review of the literature was undertaken to identify data pertaining to the incidence, pathophysiology, risk factors and management of DAOSD. A critical review of this literature was used to inform a decision framework for dupilumab-prescribers and develop a graded severity scoring tool to guide appropriate management options. RESULTS: DAOSD typically emerges within 4 months of commencing dupilumab and the occurrence of new events diminishes over time. The reported incidence varies widely depending on the nature and source of the data: 8.6-22.1% (clinical trials programme), 0.5-70% (real-world data; differences in study size, duration of follow-up, ophthalmologist intervention, use of prophylaxis). Occurrence increases with AD severity and in patients with prior history of ocular disease; pathophysiology is still to be fully characterised. Management options have evolved over time and include lubricants/artificial tears, corticosteroids, calcineurin inhibitors, antihistamines, anti-inflammatory agents and antimicrobial agents. Current therapies aim to resolve symptoms or reduce severity to levels sufficiently tolerable to enable continuation of dupilumab therapy. CONCLUSIONS: Recommendations for DAOSD assessment and management include identification of high-risk patients, vigilance for red flags (keratoconus, herpetic and bacterial keratitis), regular assessment of symptom severity (before and during dupilumab therapy), conservative management of mild DAOSD by the prescribing physician and ophthalmologist referral for collaborative care of moderate-severe DAOSD and high-risk patients.

Hydroxychloroquine Dose per Ophthalmology Guidelines and the Risk of Systemic Lupus Erythematosus Flares.

This study of an academic medical center patient cohort with systemic lupus erythematosus (SLE) investigates the association between hydroxychloroquine dose based on current guidelines and risk of lupus flares.

Prediction of serious eye damage or eye irritation potential of compounds via consensus labelling models and active learning models based on uncertainty strategies.

Serious eye damage and eye irritation have been authenticated to be significant human health issues in various fields such as ophthalmic pharmaceuticals. Due to the shortcomings of traditional animal testing methods, in silico methods have advanced to study eye toxicity. The models for predicting serious eye damage and eye irritation potential of compounds were developed using 2299 and 5214 compounds, respectively. The 40 global single models and 40 local models were developed by combining 5 molecular description methods and 4 machine learning methods. The 40 active learning models were developed by adopting uncertainty-based active learning strategies and taking local models as initial models. The 110 global consensus models based on 40 global single models were developed using a consensus strategy. Active learning models and global consensus models performed high prediction accuracy. The test accuracy of the best serious eye damage model and eye irritation model reached 0.972 and 0.959, respectively. The applicability domains for all models were calculated to verify the rationality of prediction effect. In addition, 8 structural alerts probably causing serious eye damage or eye irritation were sought out. The prediction models and structural alerts contributed to providing hazard identification and assessing chemical safety.

Los hallazgos oculares relacionados con el uso de bisfosfonatos orales / The ocular findings related to oral bisphosphonate use

Objetivo Nuestro objetivo fue investigar los hallazgos de afectación ocular en pacientes femeninas con osteoporosis que usaban bisfosfonato oral (BP). Métodos Se incluyó en el estudio a un total de 51 pacientes con osteoporosis, de 50 a 75 años, que utilizaron BP oral durante al menos un año para el grupo de estudio y a 64 pacientes sin osteoporosis de la misma edad para el grupo de control, todas del sexo femenino. Se anotaron el tipo de BP y el tiempo de exposición. Se evaluaron los resultados del examen oftálmico de las pacientes que recibieron BP oral por osteoporosis y de las controles. Resultados La duración media del uso de BP fue de 3,96 años. Se detectó que 4de 51 pacientes fueron diagnosticadas con disfunción de la glándula de Meibomio (7,8%), 7de 102 ojos tenían margen palpebral eritematoso, irregular, engrosado o telangiectasia alrededor de los orificios glandulares. No hubo hallazgos patológicos en el examen del fondo de ojo. El valor medio de las medidas del brote (ph/ms) fue de 7,90±7,96 en el grupo de estudio y de 5,02±0,81 en el grupo de control. Cuando se compararon los valores medios, hubo una diferencia significativa entre los 2grupos (p=0,001). Se encontró una diferencia significativa en el valor medio de las mediciones del flare entre las pacientes que usaban alendronato e ibandronato y las del grupo de control (p=0,001; p=0,005, respectivamente). Conclusión Nuestro estudio mostró que el flare de la cámara anterior asociado con la inflamación crónica del ojo se puede observar con mayor frecuencia en pacientes que usan alendronato e ibandronato por vía oral en comparación con aquellos que no lo hacen. Además, se puede decir que BP oral puede provocar efectos secundarios oculares similares a los de la BP intravascular (AU)

Objective We aimed to investigate ocular involvement findings in female osteoporosis patients using oral bisphosphonate (BP). Methods A total of 51 female osteoporosis patients aged 50-75 years using oral BP for at least one year for the study group and 64 age-matched non-osteoporosis female patients for the control group were included in the study. The BP type and exposure time were noted. The ophthalmic examination findings and measurements of the flare of the patients who received oral BP due to osteoporosis and the controls were evaluated. Results The mean duration of BP use was 3.96 years. In the study group, it was detected 4of 51 patients were diagnosed with meibomian gland dysfunction (MGD) (7.8%), 7of 102 eyes had erythematous, irregular, thickened lid margin or telangiectasia around the glandular orifices. There were no pathological findings on fondus examination. The mean value of measurements of the flare (ph/ms) was 7.90±7.96 in the study group, and 5.02±0.81 in the control group. When the mean values were compared, there was a significant difference between the 2groups (P=0.001). A significant difference was found in the mean value of measurements of the flare between the patients using alendronate, and ibandronate with the control group (P=0.001; P=0.005, respectively). Conclusion Our study showed that the flare in the anterior chamber associated with chronic ocular inflammation can be seen higher rate in patients using oral alendronate, and ibandronate compared to those who do not. Morever it can be said that oral BPs may cause similar ocular side effects like as intravascular BPs (AU)

Eye disorders associated with newer antiepileptic drugs: A real-world disproportionality analysis of FDA adverse event reporting system.

BACKGROUND: Newer antiepileptic drugs such as levetiracetam, lacosamide, topiramate, gabapentin, oxcarbazepine, lamotrigine, and zonisamide are prescribed by physicians for the treatment of epilepsy. These drugs are also associated with a series of eye disorders. However, very few studies have systemically compared eye disorders associated with newer AEDs in a large sample of patients diagnosed with epilepsy. OBJECTIVE: This study aimed to evaluate the association between eye disorders and several newer AEDs, and also to examine the differences in the frequency of adverse events across individual AEDs through data mining of the self-reporting US Food and Drug Administration Adverse Event Report System (FAERS) database. METHODS: The definition relied upon system organ class and preferred terms according to the Medical Dictionary for Regulatory Activities. Disproportionality analysis was used to detect the risk signals from the FAERS database. The proportional reporting ratio, and χ2 (chi-square) values were calculated to assess the association between AEs and AED use. RESULTS: FAERS reports for 158,095 cases from January 1 of 2015 to September 30 of 2020 were included. AEDs were associated with a series of eye-related AEs that were defined by 106 preferred terms and could be classified into 10 aspects. CONCLUSION: There is variation in the types and severity of eye-related AEs across individual AEDs. Typically, topiramate and lamotrigine are more likely to cause serious eye-related AEs. In contrast, lacosamide rarely results in any severe eye-related AEs, and only diplopia and metamorphopsia are significant. levetiracetam tends to produce ocular neuromuscular disorder-related AEs. Macula-related AEs are associated with gabapentin. zonisamide appears to be closely associated with choroidal effusion and angle-closure glaucoma. oxcarbazepine is primarily associated with several cornea-related AEs.

Role of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases.

BACKGROUND: AMP-activated protein kinase (AMPK) plays a precise role as a master regulator of cellular energy homeostasis. AMPK is activated in response to the signalling cues that exhaust cellular ATP levels such as hypoxia, ischaemia, glucose depletion and heat shock. As a central regulator of both lipid and glucose metabolism, AMPK is considered to be a potential therapeutic target for the treatment of various diseases, including eye disorders. OBJECTIVE: To review all the shreds of evidence concerning the role of the AMPK signalling pathway in the pathogenesis of ocular diseases. METHOD: Scientific data search and review of available information evaluating the influence of AMPK signalling on ocular diseases. RESULTS: Review highlights the significance of AMPK signalling in the aetiopathogenesis of ocular diseases, including cataract, glaucoma, diabetic retinopathy, retinoblastoma, age-related macular degeneration, corneal diseases, etc. The review also provides the information on the AMPK-associated pathways with reference to ocular disease, which includes mitochondrial biogenesis, autophagy and regulation of inflammatory response. CONCLUSION: The study concludes the role of AMPK in ocular diseases. There is growing interest in the therapeutic utilization of the AMPK pathway for ocular disease treatment. Furthermore, inhibition of AMPK signalling might represent more pertinent strategy than AMPK activation for ocular disease treatment. Such information will guide the development of more effective AMPK modulators for ocular diseases.[Formula: see text].

Identification of Risk Factors for Dupilumab-associated Ocular Surface Disease in Patients with Atopic Dermatitis.

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface disease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupilumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30-11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis.