A case report of paracentral acute middle maculopathy after Ad26.COV2.S administration

¹Ophthalmology Department, Port Elizabeth Provincial Hospital, Gqeberha, South Africa

^&Corresponding author
Jonathan Timothy Oettlé, Ophthalmology Department, Port Elizabeth Provincial Hospital, Gqeberha, South Africa

Introduction    

Paracentral Acute Middle Maculopathy (PAMM) was first described in 2013 [1]. Initially thought to be a more superficial variant of Acute Macular Neuroretinopathy (AMN), it is now considered a separate entity with overlapping features [2]. Paracentral acute middle maculopathy is a descriptive diagnosis of optical coherence tomography findings, featuring placoid hyperreflective band-like lesions at the level of the inner nuclear layer (INL) [2]. Various morphological patterns have been described and the disease may be isolated or associated with other systemic conditions or vascular risk factors [2,3]. Clinically, patients present with blurred vision and scotomas, which are usually negative [2]. The underlying mechanism is proposed to be localised retinal capillary ischaemia at the level of the intermediate plexus [4]. Paracentral Acute Middle Maculopathy has been reported after SARS-CoV-2 infection [5,6], after administration of other SARS-CoV-2 vaccines [7,8], as well as after other viral illnesses and vaccines including H1N1 and influenza [3]. This report describes a case of PAMM after Ad26.COV2.S vaccine from South Africa.

Patient and observation     

Patient Information: a 60-year-old male was referred to our optometry screening service with a complaint of painless blurred vision in the left eye. His symptoms were noted on waking, the morning after having received the Ad26.COV2.S (J&J) vaccine from a primary health care facility. There was no headache or other symptoms of giant cell arteritis. He had a background medical history of systemic hypertension and epilepsy, for which he was taking enalapril 20mg/d, sodium valproate 500mg BD, aspirin 300mg/d and folate 5mg/d. His blood pressure was 150/97; last seizure was in March 2020. He was a non-smoker and did not drink alcohol. He was diagnosed with SARS-CoV-2 on a PCR test 8 weeks prior to receiving his vaccine, and did not require hospitalization. He had no prior history of vaccine related adverse events.

Clinical findings: on presentation, the patient had 6/6 vision in the unaffected right eye, and 6/18 in the left eye. Pupillary responses were normal, intraocular pressure (IOP) 18 mmHg Oculus Dexter (OD) and 17mmHg Oculus Sinister (OS). No abnormalities were noted on slit-lamp examination. The cup-to-disc ratio was 0,3 OU. Optic nerve function tests showed dyschromatopsia, decreased contrast sensitivity and decreased light brightness in the affected eye. Amsler grid demonstrated a scotoma but no metamorphopsia.

Timeline of events: the patient received his vaccine in the afternoon of 21/10/2021, and noted symptoms upon waking on 22/10/2021 - approx 18 hours later. He presented to a community health center on 02/11/2021, and was referred to our optometry screening service, at which time the initial optical coherence tomography (OCT) and Blue-light fundus autofluorescence (BAF) was done. The patient was then seen at eye clinic on 22/11/2021, where the diagnosis was made and OCT and BAF repeated. The patient was seen again on 25/11/2021; 24/2 visual fields were done, blood was taken, and a local private ophthalmology practice was contacted who kindly agreed to do a fluorescein angiogram for us. Chest X-ray and Electrocardiogram (ECG) were unremarkable. Carotid doppler ultrasound was delayed, and could only be performed on 09/02/2022; it was unremarkable. On review 7/12/2021 the patient was noted to have a total serum cholesterol of 6,01, other blood investigations were within normal limits. By this visit the vision had deteriorated to counting fingers, and OCT demonstrated thinning of the INL. 24/2 and 10/2 visual field analysis were done, this showed marked progression of the scotoma and significant superior hemifield loss. On review at 14/02/2022 the vision had stabilized; clinical examination and special investigations were repeated (Table 1).

Diagnostic assessment: OCT: 02/11/2021 - OD: no abnormalities. OS: multiple hyperreflective band-like lesions at the INL in a paracentral distribution (Figure 1). 22/11/2021 - lesions resolving with thinning and irregularity of INL (Figure 2). 07/12/2021 - hyperreflective band-like scarring and thinning of INL (Figure 3). 14/02/2022 - OS: loss of retinal architecture, partial loss of foveal contour, photoreceptor disruption, thinning and atrophy of middle retinal layers parafoveally. BAF: 02/11/2021 - OD: no abnormalities. OS: multiple hypoautofluorescent lesions confined to the central macula in a reticular pattern (Figure 4). 22/11/2021 - lesions resolving, subtle mottling remains. 14/02/2022 - no change from above. FA: 13/12/2021 - unremarkable. Normal perfusion, no leakage or areas of hypo- or hyperfluorescence. Colour fundus photograph: 13/12/2021 - unremarkable (Figure 5). Visual field tests: 25/11/2021 - OD: normal. OS: 24/2 = pattern deviation showed mild field loss. 07/12/2021 - OD: normal. OS: 24/2 = significant worsening with profound field loss in superior hemisphere. 10/2 = marked central and paracentral field loss. 14/02/2022 - OS: stabilization of field loss, no further deterioration (Figure 6). Blood tests: 25/11/2021 - UEC, FBC, HbA1C, Ca, Mg, Phos, LFT´s, Chol., ESR, CRP, thyroid functions, autoimmune screen, syphilis serology - unremarkable except for slightly raised cholesterol. Chest X-ray: 25/11/2021 - unremarkable. Electrocardiogram (ECG): 25/11/2021 - normal sinus rhythm. Carotid doppler: 09/02/2021 - unremarkable

Therapeutic intervention: no specific treatment was given for PAMM. Our patient was initiated on Simvastatin 20mg nocte upon identification of raised serum cholesterol.

Follow up and outcome: during follow up at our eye clinic a progressive decline in visual acuity was noted, which stabilised at counting fingers (LogMAR 2.00). As there is no known therapeutic intervention for PAMM, investigations were primarily aimed at identifying underlying vascular risk factors and excluding conditions with systemic implications, such as giant cell arteritis or a reperfused central retinal artery occlusion.

Patient perspective: “I am more than happy with the care received by the doctors and nurses at the eye clinic, they have exceeded my expectations.”

Informed consent: after counselling, the patient gave informed consent for the use of anonymised clinical data and images.

Discussion     

Vaccines remain our best protection against SARS-CoV-2 infection, hospitalisation and death [9]. A lack of effective therapies for treating symptomatic SARS-CoV-2 infection has triggered a vaccine race, with 259 vaccine projects underway from November 2020 [10]. The rapid pace of vaccine development and regulatory approval has increased the risk for vaccine safety adverse events [11], and healthcare providers should be vigilant to identify and report adverse vaccine events. Paracentral Acute Middle Maculopathy (PAMM) was initially described by Saraf et al. in 2013 as a superficial variant of Acute Macular Neuroretinopathy (AMN), but is currently thought to be a distinct entity with overlapping features with AMN. Both PAMM [5,6] and AMN [12] have been reported after SARS-CoV-2 infection, the proposed mechanism is a result of vascular, inflammatory and neuronal changes triggered by the virus [8], possibly with a thrombotic milieu involving the capillary plexus [6]. Vinzamuri et al. described a case of bilateral PAMM after ChAdOx1 nCoV-19 vaccine, also an adenovirus vector vaccine. Both Vaccine Induced Thrombosis with Thrombocytopenia Syndrome (VITT/TTS) and microvascular changes such as capillary leakage have been reported after ChAdOx1 nCoV-19 and Ad26.CoV2.S vaccines [13], suggesting a similar underlying pathophysiological mechanism.

Pichi et al reported a case of suspected PAMM after SinoPharm (BBIBP-CorV) vaccine administration, an inactivated vaccine that does not use an adenovirus vector; this case was also associated with systemic side effects (uncontrolled hypertension). Administering a vaccine in a patient who has previously had a SARS-CoV-2 infection results in a heightened immune response [14] and an increased incidence of systemic symptoms [15]; this may have been a contributing factor in our case. Acute macular neuroretinopathy has been described after Ad26.CoV2.S [16], ChAdOx1 [17] and BBIBP-CorV [7] vaccines, and likely represents a similar disease process. Our report describes the 3^rd reported case of PAMM after a SARS-CoV-2 vaccine, and the first after Ad26.CoV.2.S. Due to the small number of cases reported in the literature, it is impossible to know the typical history or prognosis for patients with vaccine-related PAMM; our patient had considerably worse visual outcomes than those reported previously. Reasons for the increased severity of disease may include the presence of underlying vascular risk factors, namely systemic hypertension and undiagnosed hypercholesterolaemia, and the recent SARS-CoV-2 infection. The temporal association in this and similar cases suggest that Ad26.CoV2.S may trigger a microvascular or thrombotic pathway, but causation cannot be inferred on the basis of a single case. Vigilance in reporting ocular adverse effects is key to better understanding the impact of Ad26.CoV2.S and other SARS-CoV-2 vaccines in the eye. Strengths of the study were a prompt diagnosis and a willing and involved patient. Limitations included resource constraints, lack of more sophisticated special investigations, delays in accessing the eye clinic and delays in obtaining special investigations.

Conclusion     

We report a case of unilateral paracentral acute middle maculopathy shortly after Ad26.CoV2.S administration.

Competing interests     

The author declares no competing interests.

Authors' contributions     

The author have read and agreed to the final manuscript.

Acknowledgements     

The author gratefully acknowledges Dr T. Van Niekerk for supervising the project.

Table and figures     

Table 1: timeline of events

Figure 1: optical coherence tomography: left eye 02/11/2021

Figure 2: optical coherence tomography: left eye 22/11/2021

Figure 3: optical coherence tomography: left eye, 07/12/2021

Figure 4: blue-light fundus autofluorescence: left eye, 02/11/2021

Figure 5: colour fundus photograph: left eye, 13/12/2021

Figure 6: visual field: left eye, 14/02/2022

References