Risk of Corneal Graft Rejection and Vaccination: A Matched Case-Control Study From a United States Integrated Health Care System.

PURPOSE: Data on vaccine-associated corneal transplant rejections are limited. We examined the association between graft rejection and vaccination. DESIGN: Matched case-control METHODS: We used electronic health records to identify corneal transplant recipients between January 2008 and August 2022 at Kaiser Permanente Southern California. Cases were transplant recipients who experienced a graft rejection (outcome) during the study period. Randomly selected controls who did not experience a corneal graft rejection at their matched cases' index date (rejection date) were matched in a 3:1 ratio to cases. For controls, index date was determined by adding the number of days between transplant and graft rejection of their matched case to the control's transplant date. RESULTS: The study included 601 cases and 1803 matched controls (mean age 66 years [s.d. 17.0], 52% female, 47% non-Hispanic white). Twenty-three% of cases and 22% of controls received ≥1 vaccinations within 12 weeks prior to the index date. The adjusted odds ratio (aOR) for vaccination in the 12 weeks prior to index date, comparing cases to controls was 1.17 (95% CI: 0.91, 1.50]). The aOR was 1.09 (0.84, 1.43) for 1 vaccination, 1.53 (0.90, 2.61) for 2 vaccinations, and 1.79 (0.55, 5.57) for ≥3 vaccinations. The aOR was 1.60 (0.81, 3.14) for mRNA vaccines, and 1.19 (0.80, 1.78) for adjuvanted/high dose vaccines. CONCLUSIONS: We found no evidence to suggest an association between vaccination and graft rejection. Our findings provide support for the completion of recommended vaccinations for corneal transplant recipients, without significantly increasing the risk of graft rejection.

Viral infections and pathogenesis of glaucoma: a comprehensive review.

Glaucoma is a leading cause of irreversible blindness worldwide, caused by the gradual degeneration of retinal ganglion cells and their axons. While glaucoma is primarily considered a genetic and age-related disease, some inflammatory conditions, such as uveitis and viral-induced anterior segment inflammation, cause secondary or uveitic glaucoma. Viruses are predominant ocular pathogens and can impose both acute and chronic pathological insults to the human eye. Many viruses, including herpes simplex virus, varicella-zoster virus, cytomegalovirus, rubella virus, dengue virus, chikungunya virus, Ebola virus, and, more recently, Zika virus (ZIKV) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been associated with sequela of either primary or secondary glaucoma. Epidemiological and clinical studies suggest the association between these viruses and subsequent glaucoma development. Despite this, the ocular manifestation and sequela of viral infections are not well understood. In fact, the association of viruses with glaucoma is considered relatively uncommon in part due to underreporting and/or lack of long-term follow-up studies. In recent years, literature on the pathological spectrum of emerging viral infections, such as ZIKV and SARS-CoV-2, has strengthened this proposition and renewed research activity in this area. Clinical studies from endemic regions as well as laboratory and preclinical investigations demonstrate a strong link between an infectious trigger and development of glaucomatous pathology. In this article, we review the current understanding of the field with a particular focus on viruses and their association with the pathogenesis of glaucoma.

Anterior Uveitis following COVID Vaccination: A Summary of Cases from Global Reporting Systems.

PURPOSE: COVID-19 vaccines are currently undergoing long-term safety monitoring, including for ocular side effects. Uveitis following vaccination has been described previously with other vaccines and warrants evaluation for COVID-19 vaccines, especially given their widespread use. CASE REPORTS: We present two cases of patients who developed anterior uveitis following the Moderna COVID-19 vaccine, as reported to the National Registry for Drug-Induced Ocular Side Effects. We also summarize reports of anterior uveitis following COVID-19 vaccination as reported to the World Health Organization global database of individual case safety reports. CONCLUSIONS: Based on the temporal pattern of ocular inflammation following vaccine delivery in these cases, an association may be present between uveitis and COVID-19 vaccination. Further investigation to explore this association is warranted to guide patient care.

Possible Association Between Apremilast Therapy and Increased Tearing.

PURPOSE: To evaluate a possible association between apremilast and increased tearing. METHODS: A retrospective observational case series in which reports from VigiBase, the World Health Organization global database of Individual Case Safety Reports, and the literature involving apremilast were evaluated by the National Registry of Drug-Induced Ocular Side Effects for possible increased tearing. RESULTS: A total of 45 cases of possible apremilast-induced increased tearing were identified. All patients were on the standard dose of 30 mg BID. There was no sex difference and ages ranged from 28 to 77 years with an average of 56 years ± 12. Time to onset of the increased tearing ranged from a few days to many months. There were 10 cases of positive dechallenge, 3 cases of positive rechallenge, and 1 case with double-positive rechallenge. In the cases with positive dechallenge and rechallenge, the increased tearing resolved as early as within 2 days after stopping the drug. Most cleared within 2 weeks. One case required 3 months for tearing to return to normal. CONCLUSIONS: Based on patterns and positive dechallenge and rechallenge data, apremilast possibly causes increased tearing on rare occasions.

Corrigendum to "The Role of Medications in Causing Dry Eye".

[This corrects the article DOI: 10.1155/2012/285851.].

Oral Anti-Vascular Endothelial Growth Factor Drugs and Ocular Adverse Events.

PURPOSE: To evaluate possible associations between oral anti-vascular endothelial growth factor (VEGF) drugs and ocular side effects. METHODS: Spontaneous reports were collected and evaluated by the National Registry of Drug-Induced Ocular Side Effects on the three oral anti-VEGF drugs (pazopanib, sorafenib, and sunitinib) for possible ocular side effects. RESULTS: Reported side effects include blurred or decreased vision (389 cases); periocular or eyelid edema (273 cases); superficial anterior segment toxicity (270 cases); conjunctival, retinal, or vitreous bleeding (77 cases); retinal detachments (RDs) or retinal tears (RTs) (75 cases); extraocular muscle disorders, including ptosis (51 cases); discoloration of eyelashes (36 cases); retinal arterial or venous occlusions (26 cases); optic nerve disorders, including papilledema and ischemic optic neuropathy (21 cases); uveitis (10 cases); and macular edema (7 cases). Spontaneous reports of possible RD or RT have been associated with pazopanib (31 RDs and 12 RTs), sunitinib (24 RDs and 0 RT), and sorafenib (7 RDs and 2 RTs). CONCLUSIONS: Oral anti-VEGF drugs can cause superficial anterior segment side effects. Pazopanib has been reported to be possibly linked to RDs and RTs. This study suggests that sorafenib and sunitinib are suspected as well. RDs were seldom differentiated into rhegmatogenous retinal detachments (RRDs) or non-RRDs. The association of oral anti-VEGF drugs with RRD and RT are unclassified although this suggests a "signal" requiring further study. The association of oral anti-VEGF drugs with serous retinal detachments, while rare, is plausible. Patients on this class of drugs should be instructed to seek immediate ophthalmic consultation if retinal symptoms occur.

Atypical Optic Neuritis After Inactivated Influenza Vaccination.

The existence of vaccine-associated optic neuritis is essentially based on the temporal relationship between the administration of a vaccine and the development of optic neuritis in patients with no other known aetiologies for infectious or non-infectious inflammation that could account for the optic neuritis. Influenza vaccine (inactivated or live attenuated) is considered to be one of vaccines that could be related to optic neuritis. The authors describe a rare case of bilateral asymmetric optic neuritis with leptomeningeal enhancement on magnetic resonance imaging (MRI) in a previously healthy young woman who received inactivated influenza vaccination 2 weeks before the onset of symptoms.

Liquid Nitrogen Cryotherapy Treatment of Herpes Simplex Epithelial Keratitis.

A retrospective case series was performed in a university setting for all patients with herpes simplex epithelial keratitis who underwent liquid nitrogen cryotherapy from 2012-2015. Outcome measure was clinical evidence of resolution of epithelial keratitis in the cornea with re-epithelialization. All cases of epithelial keratitis showed partial and complete resolution at day 1 and week 1 respectively. Liquid nitrogen cryotherapy is a safe and effective treatment for herpes epithelial keratitis comparable to other published studies.

Vaccine-Associated Uveitis.

All of the widely administered vaccines have been reported to cause uveitis. The ocular inflammation is usually temporary and resolves with topical ocular steroids. During a 26-year period, a total of 289 cases of vaccine-associated uveitis were reported to three adverse reaction reporting databases. Hepatitis B vaccine, either alone or administered with other vaccines, appears to be the leading offender. Clinicians are encouraged to report cases of vaccine- or drug-associated ocular adverse reactions to www.eyedrugregistry.com.

Association Between Bortezomib Therapy and Eyelid Chalazia.

IMPORTANCE: Spontaneous reports to the National Registry of Drug-Induced Ocular Side Effects and case reports in the literature suggest an association between bortezomib use and chalazia. OBSERVATIONS: To our knowledge, there have been 24 reports of bortezomib-associated chalazia. Fourteen reports were collected from the National Registry of Drug-Induced Ocular Side Effects. These reports originated at the US Food and Drug Administration's Adverse Event Reporting System or at the World Health Organization's Uppsala Monitoring Centre. An additional 10 case reports were found in the literature. The mean age of the 24 patients was 61 years (age range, 37-79 years), 8 were female and 11 were male (the sex was unknown in 5), and the mean duration of bortezomib therapy before the onset of chalazia was slightly more than 3 months (range, 26-428 days; mean, 98 days). Chalazia were usually multiple and involved the upper eyelid. Recommendations for the bortezomib dosages were within the package insert. Most patients were receiving multiple medications. There were 8 positive dechallenge case reports and 3 positive rechallenge case reports. CONCLUSIONS AND RELEVANCE: Using the World Health Organization's classification for adverse drug reactions, the association between bortezomib use and chalazia is classified as possible. This conclusion is based on the finding that chalazia improved or resolved in most patients when bortezomib was discontinued, the temporal relationship between initial administration of bortezomib and chalazia onset, and the positive dechallenge and rechallenge data.

Dry eye in LASIK patients.

BACKGROUND: Increasing age is a known risk factor for developing dry eye. The specific aims of the present study were to determine the prevalence of dry eye syndrome (DES) and use of post-operative dry eye medications in a relatively young population presenting for LASIK surgery at an academic ophthalmology clinic. FINDINGS: A retrospective, analysis of 948 de-identified patient charts (median age 39 years, not age stratified) was performed to extract pre-LASIK diagnoses and post-LASIK medication lists. Clinical evaluation for DES and the results of Schirmer's reflex tear flow test were used to assign LASIK patients into Normal, Pre-dry eye (Pre-DES), and Dry Eye Syndrome (DES) groups; which were then compared for use of dry eye medications.Based on pre-operative diagnoses, only 2% (CI: 1.3 - 3.1) of LASIK patients presented with overt DES. Unexpectantly, 25% (CI: 22.2 - 27.6) of LASIK patients labeled Pre-DES were not classified by the clinician as having overt DES, yet they showed poor reflex tear flow rates ≤ 5 mm before surgery, and frequently used post-operative lubricant dry eye medications. CONCLUSIONS: Although the number of patients with pre-existing eye conditions was unknown, a sizable portion of relatively young LASIK patients displays poor reflex tear flow without overt DES. Such patients could go on to develop more serious consequences of poor tear flow, such as corneal abrasion and erosion. More specific, dry eye medications may be needed for ideal treatment.

Human papilloma virus vaccine associated uveitis.

PURPOSE: To report a possible association between human papilloma virus (HPV) vaccination and uveitis. METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side effects, World Health Organization and Food and Drug Administration were collected on uveitis associated with human papilloma virus vaccination. A MEDLINE search was performed using keywords "uveitis," "iritis," "iridocyclitis," "human papilloma virus," "Cervarix", and "Gardasil." MAIN OUTCOME MEASURES: Data garnered from spontaneous reports included the age, gender, adverse drug reaction (ADR), date of administration, concomitant administration of other vaccinations, time until onset of ADR, other systemic reactions, and dechallenge and rechallenge data. RESULTS: A total of 24 case reports of uveitis associated with human papilloma virus vaccination were identified, all cases were female, and the median age was 17. Median time from HPV vaccination to reported ADR was 30 days (range 0-476 days). DISCUSSION: According to World Health Organization criteria, the relationship between human papilloma virus vaccination and uveitis is "possible." Causality assessments are based on the time relationship of drug administration, uveitis development and re-challenge data. CONCLUSIONS: Clinicians should be aware of a possible bilateral uveitis and papillitis following HPV vaccination.

Conjunctival and corneal ulceration associated with nicorandil.

CONTEXT/OBJECTIVE: To report an association between conjunctival and corneal ulceration and nicorandil therapy for angina. METHODS: Review of the literature and spontaneous reports collected at the National Registry of Drug-Induced Ocular Side Effects (Portland, Oregon), the FDA Spontaneous Reporting System (Bethesda, Maryland) and the World Health Organization's Uppsala Monitoring Center (Uppsala, Sweden). RESULTS: Thirteen case reports of adverse ocular reactions were collected. Abnormal vision (5 reports), corneal ulcer (4 reports) and conjunctival ulcer (4 reports) were associated with nicorandil. Eight subjects were male and 5 female with an average age of 75.4 ± 8.3 years. The average duration of therapy to development of the ADR was 30.4 days ±3 days. Eleven case reports had positive dechallenge and the patients fully recovered. The average dose was 21.6 mg daily. CONCLUSION: Using WHO classification for adverse drug reactions, the association between nicorandil and conjunctival and corneal ulceration is "possible". The case reports indicate that, if recognized, withdrawing nicorandil will lead to resolution of the conjunctival or corneal ulceration. Advanced age and accumulation of nicotinic acid in tissues may be contributory to the risk of developing ocular ulcerations from nicorandil.

Toxicity of topical ophthalmic anesthetics.

INTRODUCTION: Topical ocular anesthetics are generally well tolerated in clinical settings but have great potential for abuse if used by patients at home. This abuse can lead to significant ocular complications. Topical ocular anesthetic abuse can lead to superficial punctate keratitis, persistent epithelial defects, stromal/ring infiltrates, corneal edema, endothelial damage and ocular inflammation, even when used in a dilute concentration. Patient characteristics may include a healthcare association and/or psychiatric illness. In these instances, patients often do not admit to anesthetic use and are often initially treated for acanthamoeba keratitis. Local anesthetics are thought to cause direct toxicity to the corneal epithelium, stroma and endothelium. This in turn may lead to release of antigens and from there an inflammatory response in the form of infiltrate and edema. It is thought that preservatives in anesthetics may play a further role in toxicity. AREAS COVERED: The authors provide a brief history on topical ocular anesthetics and review the most recent literature on reported ocular toxicities of topical anesthetics. EXPERT OPINION: Practitioners must maintain high suspicion for topical ocular anesthetic abuse to identify it early. Topical ocular anesthetic abuse is often misdiagnosed as acanthamoeba keratitis. Early identification is one of the most important factors for a successful outcome. It is also imperative to give proper alternative pain control to avoid topical anesthetic abuse.