A clinical case of bilateral posterior scleritis associated with consecutive panuveitis following the influenza vaccine

Posterior scleritis (PS) is a potentially sight-threatening inflammation of the sclera located behind the ora serrata. Variable clinical presentation and low incidence rates make PS a complex ophthalmologic diagnosis, and it is an often underdiagnosed disease that can lead to many ocular complications. Associated anterior uveitis is a common clinical sign of PS,1Benson WE Posterior scleritis.Surv Ophthalmol. 1988; 32: 297-316Google Scholar but in some severe cases it can progress to diffuse panuveitis (PU). There has been growing awareness recently regarding immune-mediated reactions to vaccinations. Adverse events seen with the influenza vaccine remain low, and ocular events are exceptional. Prior literature has documented cases of isolated PS or PU following influenza vaccination,2Thurairajan G Hope-Ross MW Situnayake RD Murray PI Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine.Rheumatology. 1997; 36: 120-123Google Scholar but no prior literature reported a case of concomitant PS and PU following any type of vaccine, to our knowledge. We report a case of bilateral PS complicated by concurrent PU following the 2022 Fluzone Quadrivalent influenza vaccine (Sanofi Pasteur Inc, Bridgewater, NJ). A 67-year-old white female with no pertinent medical or ocular history presented with headache and ocular pain 24 hours after administration of the Fluzone Quadrivalent inactivated influenza vaccine. Floaters appeared in her vision another 48 hours later. Initially, the patient consulted an optometrist, who referred her to a glaucoma specialist for bilateral ocular hypertension. Two weeks after the start of symptoms, the patient was diagnosed with glaucoma, and bimatoprost was prescribed. A week later, the patient presented to the ophthalmology emergency department due to worsening of her condition despite treatment compliance. She was now reporting bilateral decreased visual acuity (VA) in addition to the initial symptoms. The patient at this time had a VA of 20/50+1 OD and 20/150+1 OS without correction, mild cataracts OU, quiet anterior chambers OU, presence of 1+ vitreous cells OU, and an intraocular pressures of 22 mm Hg OD and 19 mm Hg OS. Dilated fundus examination showed floaters and diffuse macular hyperautofluorescence OU suggestive of intermediate and posterior uveitis, respectively. Optical coherence tomography showed choroidal folds, subretinal fluid, scleral thickening, and vitreous opacities (Fig. 1). B-scan ultrasound demonstrated the pathognomonic T-sign bilaterally confirming PS. An oral nonsteroidal anti-inflammatory drug was prescribed as well as an autoimmune, inflammatory, and infectious work-up (i.e., complete blood count, erythrocyte sedimentation rate, C-reactive protein, antinuclear antibodies (ANAs), angiotensin-conversion enzyme, lysozyme, antineutrophil cytoplasmic antibodies (ANCAs), human leukocyte antigens B27, QuantiFERON-TB Gold (Quiagen, Germantown, MD), venereal disease research laboratory test and fluorescent treponemal antibody absorption test for syphilis; rheumatoid factor, anti-citrullinated protein antibodies, and a chest x-ray). A 48-hour follow-up was scheduled, and an urgent referral to the uveitis clinic also was made. The patient did not present to her scheduled follow-up and instead was seen a week later, now reporting new floaters. VA was 20/500 OD and hand motion OS without correction, intraocular pressure was 27 mm Hg OD and 20 mm Hg OS, dilated fundus examination showed increased vitreous opacities (Fig. 2), and optical coherence tomography showed increased subretinal fluid. Autoimmune and infection disease work-up was negative except for a non-significantly increased ANAs. An additional extensive autoimmune work-up also was ordered by a rheumatologist (i.e., hepatitis B and C serology, HIV serology, rheumatoid factor, cytoplasmic ANCAs, perinuclear ANCAs, thyroid-stimulating hormone, anti-proteinase 3, antibodies directed against myeloperoxidase, anti-cyclic citrullinated peptides, antibodies against extractable nuclear antigens, double-stranded DNA, soluble ANAs, and protein electrophoresis). This additional work-up did not yield more evidence of autoimmune disease. Oral prednisone and brinzolamide-timolol eyedrops OU were prescribed. Three days later, the vitreoretinal diseases specialist diagnosed a progression of the posterior uveitis into PU, so prednisolone acetate 1% eyedrops were added. All subsequent follow-ups demonstrated a favourable response to treatment and a resolution of symptoms. At last follow-up 30 days after starting oral prednisone, the fundus showed resolution of choroidal folds OU, and final VA was 20/40 OD and 20/20 OS. The thickness map also objectified decreased scleral thickness and resolution of subretinal fluid OU. With the advent of mass vaccination campaigns, there has been lately a growing awareness of possible rare adverse events. We report a case of bilateral PS with concomitant PU following the 2022 Fluzone Quadrivalent vaccine. To our knowledge, this is the first case of bilateral PS associated with bilateral PU following an influenza vaccine reported in the literature. Reports of postvaccination PS are limited. Thurairajan et al.2Thurairajan G Hope-Ross MW Situnayake RD Murray PI Polyarthropathy, orbital myositis and posterior scleritis: an unusual adverse reaction to influenza vaccine.Rheumatology. 1997; 36: 120-123Google Scholar were the first and only to report a case of bilateral PS following the 1993 Fluvirin inactivated influenza vaccine (CSL Seqirus, Holly Springs, NC). No subsequent paper mentioned other cases of PS following influenza vaccination. Severe intraocular inflammation in association with influenza vaccination was reported in only a few patients with bilateral PU following the influenza vaccine.3Manusow JS Rai A Yeh S Mandelcorn ED Two cases of panuveitis with orbital inflammatory syndrome after influenza vaccination.Can J Ophthalmol. 2015; 50: e71-e74Google Scholar,4Wells MB Garg S Bilateral panuveitis after influenza vaccination.Retin Cases Brief Rep. 2009; 3: 386-387Google Scholar No patients reported simultaneous PS and PU bilaterally after vaccination. PS is usually associated with systemic disease such as rheumatoid arthritis. Bilateral PS represents approximately 10%–33% of all cases and about 80% of autoimmune cases.1Benson WE Posterior scleritis.Surv Ophthalmol. 1988; 32: 297-316Google Scholar In addition to being a rare case of bilateral PS without underlying autoimmunity, our patient also had no ocular history compared with reports of PU after the influenza vaccine.3Manusow JS Rai A Yeh S Mandelcorn ED Two cases of panuveitis with orbital inflammatory syndrome after influenza vaccination.Can J Ophthalmol. 2015; 50: e71-e74Google Scholar,4Wells MB Garg S Bilateral panuveitis after influenza vaccination.Retin Cases Brief Rep. 2009; 3: 386-387Google Scholar A recent pathophysiologic hypothesis surrounding PS suggests that it could be caused by a type III hypersensitivity reaction from antigen–antibody immune complex deposition. In this case, the influenza vaccine may have produced a similar reaction. However, with mass vaccination campaigns, chances of adverse events also will increase without a true underlying association. This makes a causal association difficult, if not impossible, to prove in this case. In any case, this would not constitute a contraindication to influenza vaccination given the proven benefits to reducing morbidity and mortality at large. In conclusion, we report a case of bilateral PS with bilateral PU following influenza vaccine. In the absence of another identifiable infectious or inflammatory etiology, this suggests that the influenza vaccine could be a possible etiology due to temporal association. However, we acknowledge that causal association cannot be confirmed, and this could have occurred after the influenza vaccine coincidentally. Nevertheless, ophthalmologists should be aware of possible rare vaccine-related adverse events so as to inquire about recent vaccination to better counsel patients on possible prophylactic treatments for future doses. This case does not outweigh the multiple benefits of vaccination. The authors have no proprietary or commercial interest in any materials discussed in this correspondence.