Sex: F
Vaccine: VARZOS
Symptoms: Ophthalmological examination, Transplant rejection, Vision blurred
Clinical narrative: Corneal Allograft Rejection; blurring of vision in the left eye; conjunctiva had trace injection; cornea had temporal stromal and epithelial edema; 1+ cells in the anterior chamber; Eye inflammation; This case was reported in a literature article and described the occurrence of transplant rejection in a elderly female patient who received Herpes zoster (Shingrix) for prophylaxis.   Co-suspect products included Flu Seasonal QIV Dresden (Influenza vaccine Quadrivalent 2020-2021 season) for prophylaxis.   The patient's past medical history included fuchs' endothelial dystrophy (undergone Descemet stripping endothelial keratoplasty in 2010 in OD and in 2009 in OS). Previously administered products included influenza vaccine. Concomitant products included Herpes zoster (Shingrix) and Flu Seasonal QIV Dresden (Influenza vaccine Quadrivalent 2019-2020 season).   In September 2020, the patient received the 2nd dose of Shingrix and Influenza vaccine Quadrivalent 2020-2021 season. On an unknown date, 6 weeks after receiving Shingrix and Influenza vaccine Quadrivalent 2020-2021 season, the patient experienced transplant rejection (serious criteria GSK medically significant), blurred vision, conjunctival injection, corneal edema, anterior chamber cell and eye inflammation. The patient was treated with loteprednol and prednisolone acetate. On an unknown date, the outcome of the transplant rejection, blurred vision, conjunctival injection and anterior chamber cell were unknown and the outcome of the corneal edema was recovered/resolved and the outcome of the eye inflammation was recovering/resolving.   The reporter considered the transplant rejection, blurred vision, conjunctival injection, corneal edema, anterior chamber cell and eye inflammation to be possibly related to Shingrix. It was unknown if the reporter considered the transplant rejection, blurred vision, conjunctival injection, corneal edema, anterior chamber cell and eye inflammation to be related to Influenza vaccine Quadrivalent 2020-2021 season.  Additional details were reported as follows: This case was reported in a literature article and described the occurrence of Zoster subunit vaccine (RZV)-associated corneal allograft rejection, in a female patient of unspecified age, who was vaccinated with Shingrix (GlaxoSmithKline) and Unspecified Infleunza vaccine (manufacturer unknown) for prophylaxis. This case corresponds to Table 1 reported in this literature article. This case corresponds to a case reported in this literature article.  The patient was a healthy woman. The patient had undergone Descemet stripping endothelial keratoplasty in 2010 in the OD and in 2009 in the OS for Fuchs endothelial dystrophy. In 2019 (one year prior to presentation), the grafts were clear and best corrected visual acuity was 20/20 OD and 20/25 OS. The patient did not have previous history of viral keratitis or an episode of herpes zoster of any dermatome. No information on patient family history or concurrent condition or concomitant medication was reported.  In August 2020, the patient was vaccinated with first dose of Shingrix (administration route and site unknown; batch number not provided), and the second dose of Shingrix in September 2020, along with the influenza vaccine (administration route and site unknown; batch number not provided for both). The age at vaccination was not reported but it could be between 68 or 69 years at the time of vaccination. In previous years, the patient had received the influenza vaccine each fall without incident.  On an unknown date in 2020, 6 weeks after the second dose of Shingrix vaccination, the patient had blurring of vision in the left eye. At the time of onset of symptoms, the patient had been using topical loteprednol 0.5%, 1 drop 1 to 2 times per week in both eyes. At the age of 69 years, in October 2020, the patient presented with a 1-week history of blurring of vision in the left eye. At the time of the visit, visual acuity OS was 20/70. The conjunctiva had trace injection. The cornea had temporal stromal and epithelial edema, with 1+ cells in the anterior chamber. Intraocular pressure was 13 mm Hg. The patient denied systemic or local infection or trauma. The patient was diagnosed with allograft rejection. The patient was treated with prednisolone acetate 1% 8 times per day. Within 3 weeks, the anterior chamber was quiet, and after 8 weeks, the corneal edema had resolved. Vision at 3 months was 20/25 with no residual edema. Improvement of inflammation occurred quickly after intense topical steroid therapy.  The author commented "It elicits a robust immune response, with both humoral and cell-mediated responses detectable 1 month after the first dose. RZV is more immunogenic than the older ZVL. It is likely that RZV may pose a greater risk for associated immune-mediated reactions, such as reactivation of zoster keratitis and corneal allograft rejection than ZVL. Identifiable potential risk factors other than the RZV were as follows: One patient had a history of a second Descemet stripping endothelial keratoplasty in the fellow eye 10 years previously. One patient had a history of 1 previous PKP that failed because of allograft rejection. The same patient also underwent removal of 1 suture before the onset of blurred vision. One drop of topical loteprednol 0.5% was administered at the time of the suture removal, and the patient was instructed to continue his previous regimen of prednisolone acetate 1% 4 per day. The third patient had 1 episode of rejection in a previous transplant. Original indications for keratoplasty were corneal endothelial dystrophy, past trauma, and keratoconus. In 2 of the 3 cases, rejection occurred despite relatively high level of topical corticosteroid therapy: difluprednate emulsion 0.05% 3 per day (for the treatment of cystoid macular edema), in 1 patient, and prednisolone acetate 1% 4 per day, in a second patient. Improvement of inflammation occurred quickly after intense topical steroid therapy in all 3 cases. Onset of symptoms of allograft rejection occurred 5 weeks after the first RZV dose in 1 patient. In the other 2 patients, blurred vision was noted 1 and 6 weeks after the second dose. It has been reported that "overall, 30% of transplanted corneas experience at least 1 episode of immune reaction."10 Therefore, observation of a chance temporal association with RZV is possible. However, with 3 cases identified within a 3-month period, it is reasonable to consider the possibility that RZV may increase the risk for corneal allograft rejection.".  The author concluded "RZV, which elicits a more robust immune reaction than the zoster live-attenuated vaccine, ZVL, may increase the risk of allograft rejection in immunocompetent patients with preexisting corneal endothelial or penetrating transplants. Based on the available data, it may be reasonable to increase the topical corticosteroid regimen before the first dose, until approximately 3 months after the second dose of ZVL".  This is 1 of the 3 valid cases reported in this literature article.; Sender's Comments:  US-GLAXOSMITHKLINE-US2021GSK167260:Same reporter