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. 2023 Dec 15;13:1307655. doi: 10.3389/fcimb.2023.1307655

Table 1.

COVID-19 and Corneal Graft Rejection.

Age Gender Risk factors Vaccine (dose) Type of corneal transplant Interval between vaccine and rejection (days) Ocular findings Treatment Graft failure/Conclusions
63M
(Balidis et al., 2021)
Repeat graft AZD122 2 (1) DSAEK 10 Stromal oedema Dexamethasone eye drops and hypertonic ointment every 2 h Yes
Approx 60M (Ghiasian et al., 2023) Not applicable (N/A) BBIBP-
CorV (1)
PK 3 Corneal oedema Topical steroid Yes
50M
(Ghiasian et al., 2023)
Previous rejection BBIBP- CorV (1) PK 11 Corneal oedema and KPs Topical steroid Yes
40M
(Ghiasian et al., 2023)
N/A BBIBP- CorV (2) PK 54 Corneal oedema and KPs None Yes
80M
(Ghiasian et al., 2023)
Previous rejection BBIBP- CorV (3) PK 6 Corneal oedema and KPs Topical and oral steroid Yes
94F
(Forshaw et al., 2022)
N/A BNT162 b2 (1) DMEK
bilateral
14 Diffuse cornea oedema and DM folds Dexamethasone/tobramycin 6x per day and hypertonic 4x per day Yes
51M
(Yu et al., 2022)
Previous rejection, glaucoma mRNA- 1273 (1) PK 3 Corneal oedema and KPs Topical steroids Yes
64F
(Balidis et al., 2021)
Repeat graft mRNA- 1273 (2) PK 7 Diffuse corneal oedema and KPs. Dexamethasone eye drops hourly and intracameral fortecortin injections Yes
63F
(Simão and Kwitko, 2022)
Previous rejection, previous LASIK Sinovac PK 1 Corneal oedema and AC
inflammation
Topical dexamethasone every hour, 0.5% timolol maleate, 0.03% bimatoprost and polydimethylsiloxane 4 times a day Yes
69M
(Balidis et al., 2021)
Diabetes on insulin AZD122 2 (1) PK 5 Corneal oedema Subconjunctival dexamethasone injections and combined oral (methylprednisolone) and topical (dexamethasone) corticosteroid therapy No
55M
(Molero-Senosiain et al., 2022)
N/A AZD122 2 (1) PK 7 Stromal oedema, DM folds, KPs Topical steroid No
28F
(Nahata et al., 2022)
N/A AZD122 2 (1) FLEK 14 Khoudadoust line, DM folds, AC
inflammation, stromal oedema
Topical prednisolone 1% hourly, topical homatropine eye drops three times and with oral methylprednisolone 50mg once daily for 1 week No
64M
(Park et al., 2023)
Previous rejection AZD122 2 (1) PK 2 Corneal oedema and KPs Topical and systemic steroid No
35M
(Parmar et al., 2021)
Previous rejection with graft neovasculari sation AZD122 2 (1) PK 4 Corneal oedema, KPs, AC
inflammation, pupil deformity
Topical prednisolone acetate 1% hourly, IV methylprednisolone for 3 days, switching to oral prednisone 60mg PO OD No
62M
(Ravichandran and Natarajan, 2021)
N/A AZD122 2 (1) PK 21 Khodadoust’s line, corneal oedema N/A N/A
18M
(Swarup and Mehta, 2023)
Young AZD122 2 (1) DALK 13 Ciliary haze, stromal oedema Topical prednisolone acetate 1% every hour, cycloplegics and lubricants No
61M
(Molero-Senosiain et al., 2022)
N/A AZD122 2 (2) PK 30 Corneal oedema and AC
inflammation
Topical steroid and IV methylprednisolone No
79M
(Rajagopal R. and Priyanka T.M., 2022)
Previous rejection AZD122 2 (2) PK 42 Stromal oedema Hourly topical steroids and oral steroids No
36F
(Mohammadzadeh M. et al., 2022)
N/A BBIBP- CorV (1) PK 2 Corneal oedema Topical betamethasone No
54F
(Mohammadzadeh M. et al., 2022)
N/A BBIBP- CorV (1) PK 7 Corneal oedema Topical betamethasone No
40M
(Ghiasian et al., 2023)
N/A BBIBP- CorV (2) PK 65 Corneal oedema and KPs Topical steroid No
20M
(Ghiasian et al., 2023)
N/A BBIBP- CorV (2) PK 117 Corneal oedema and KPs None No
15F
(Swarup and Mehta, 2023)
Young,
Neovascular isation
BBV152 (1) DALK 9 Stromal oedema Topical prednisolone acetate 1% every hour, cycloplegics and lubricants No
71M
(Crnej et al., 2021)
Smoking BNT162 b2 (1) DMEK 7 Diffuse corneal oedema Topical dexamethasone every 2 h No
40M
(Eduarda Andrade E Andrade M. et al., 2022)
N/A BNT162 b2 (1) PK 10 Subepithelial bullae, Khodadoust line and KPs Oral prednisone 20mg, hourly topical prednisolone acetate and subconjunctival dexamethasone No
15M
(Marziali et al., 2022)
Young age BNT162 b2 (1) PK 12 Conjunctival injection, DM folds, corneal oedema Topical dexamethasone sodium phosphate 2% 6x per day No
72F
(Molero-Senosiain et al., 2022)
Previous rejection BNT162 b2 (1) DSAEK 14 Diffuse corneal oedema Topical dexamethasone No
82F
(Molero-Senosiain et al., 2022)
N/A BNT162 b2 (1) DSAEK 14 Corneal oedema Topical steroid No
48F
(Molero-Senosiain et al., 2022)
Previous rejection BNT162 b2 (1) PK 30 Microcystic oedema and DM folds Topical dexamethasone No
44F
(Nioi M. et al., 2021)
N/A BNT162 b2 (1) PK 13 Diffuse corneal oedema, KPs, DM folds, AC inflammation Topical dexamethasone and Vitamin D No
66F
(Phylactou et al., 2021)
HIV (well controlled) BNT162 b2 (1) DMEK 7 Diffuse corneal oedema, KPs, AC
inflammation
Topical dexamethasone No
68F
(Rallis et al., 2022)
Previous rejection BNT162 b2 (1) PK 4 Diffuse PEEs, DM folds, corneal oedema and AC
inflammation
Topical dexamethasone and oral acyclovir No
72M
(Wasser et al., 2021)
Previous rejection BNT162 b2 (1) PK 13 Ciliary injection, DM folds, corneal oedema and KPs Oral and topical steroid No
56M
(Wasser et al., 2021)
Previous rejection BNT162 b2 (1) PK 12 Diffuse corneal oedema, KPs and AC inflammation Oral prednisone 60mg daily and topical dexamethasone hourly No
73F
(Abousy et al., 2021)
N/A BNT162 b2 (2) DSAEK
Bilateral
4 Thickened corneas with DF Prednisolone acetate 1% eye drops four times daily No
73F
(Abousy et al., 2021)
N/A BNT162 b2 (2) DSAEK
Bilateral
9 Moderate conjunctival congestion, diffuse corneal edema, KPs, and AC inflammation Prednisolone acetate 1% eye drops four times daily No
72M
(Gouvea et al., 2022)
N/A BNT162 b2 (2) KLAL and PK 30 Perilimbal engorgement and tortuosity of vessels Hourly difluprednate 0.05%
drops, tacrolimus 0.1% ointment before bed, and his oral tacrolimus was increased to 2 mg twice daily
No
83F
(Phylactou et al., 2021)
N/A BNT162 b2 (2) DMEK 21 Circumcorneal injection, AC inflammation Topical dexamethasone No
20 papers and 33 patients
(Kuziez et al., 2023)
N/A BNT162 b2 (37%)
CoronaV ac (3%), AZD122 2 (19%) mRNA- 1273
(37%) BBIBP-
CorV (25%)
PK (n=20), DMEK (n=8), DSAEK (n=7), FLEK (n=1) Mean 11.2
Median 8.5
N/A N/A 36% of eyes with rejection resolved, 19% improved, 17% showed nil improvement.
16 papers and 34 patients
(Moura-Coelho et al., 2023)
38.9% of
eyes had previous grafts
BNT162 b2 (56%)
mRNA- 1273
(24%)
AZD122 2 (26%)
Sinovac (3%)
PK (n=20), DSAEK (n=7), DMEK (n=6),
combined PK and KLAL (n=1) LR- CLAL (n=1)
Median 9 N/A The most frequently prescribed topical CS was dexamethasone 0.1% (n=13), prednisolone
acetate 1% (n=6),
betamethasone 0.1% (n=4), and difluprednate 0.05% (n=3)
77.8% resolution
13.9% graft failure
and 8.3% partial improvement.
27 papers 37 patients (Huang et al., 2022) N/A BNT162
b2 (71.4%) AZD122 2
(23.8%)
Sinovac (4.8%)
PK (n=13) DMEK (n=5) DSAEK (n=3) Mean 10
Median 7
N/A N/A Most common adverse corneal event post COVID- 19 vaccination is corneal graft rejection
46 patients and 55 eyes between December 2020 and
July 2022
(Singh R.B. et al., 2022)
N/A BNT162 b2 (74%)
mRNA- 1273
(26%)
PK (n=34), DSAEK (n=10), DMEK (n=8) DALK (n=2) CLAT (n=1) BNT162
b2 mean: 15.1
mRNA- 1273
mean: 19.3
Decreased VA (39%) corneal
oedema (20%) AC
inflammation (17%) DM
folds (17%), conjunctival hyperaemia (15%) KPs
(15%)
Topical (n=24) oral (n=4) and subconjunctivally injected (n=5) corticosteroids 37% graft failure
Longer vaccination to rejection time in patients with PKs
7 papers 9 patients
(Sen and Honavar, 2021)
N/A BNT162 b2 (77%)
AZD122 2 (33%)
N/A Mean 7 N/A N/A Most common adverse corneal event post COVID- 19 vaccination is corneal graft rejection
5 corneal papers, 7 patients N/A BNT162 b2 (80%) PKP (n=4) N/A N/A N/A Insufficient evidence to suggest causation between COVID-10
(Wang et al., 2022) AZD122 2 (20%) DMEK (n=3) vaccination and corneal graft rejection
4 papers and 6 patients
(Lee and Huang, 2021)
N/A BNT162 b2 (80%) AZD122 2 (20%) PK (n=2)
and DMEK (n=4)
Mean 14 N/A N/A Rate of ocular complications following COVID- 19 vaccinations lower than previously reported
3 corneal papers and 3 patients
(Kumari et al., 2022)
N/A BNT162
b2 and AZD122 2
PK (n=2) DMEK (n=1) N/A N/A N/A Most common adverse ocular event post COVID-19 vaccination was uveal pathology
77 cases of graft rejection over 3 years
(Busin et al., 2022)
N/A BNT162
b2, AZD122
2 and mRNA- 1273
PKPs, DSAEKS, DMEKs N/A N/A N/A Nil statistically significant increase in rejection rates during COVID-19 vaccination period
11 papers and 15 patients relating to cornea
(Haseeb et al., 2022)
N/A BNT162
b2, CoronaV ac, AZD122 2
mRNA-
PK, DALK, DMEK, DSAEK Mean 11.8 N/A N/A COVID-19
vaccination may be associated with corneal complications
1273, BBIBP-
CorV
13 papers and 21 patients N/A BNT162
b2, CoronaV ac, AZD122
2, and mRNA- 1273
PK (n=12), DMEK (n=6), DSAEK (n=4), LR- CLAL (n=1) Mean 10.4
Median 7
Corneal oedema most common clinical finding (87%) Most commonly topical steroid (52%) followed by a combination of topical and oral steroid (13%) Graft failure occurred in 39% of eyes
77F
(Balidis et al., 2021)
N/A mRNA- 1273 (1) DMEK 7 Diffuse corneal oedema and AC
inflammation
Subconjunctival dexamethasone injections and eye drops of 1 mg/mL dexamethasone and hypertonic every 2 h No
74M
(Shah et al., 2022)
N/A mRNA- 1273 (1) DMEK 7 Corneal oedema and KPs Topical prednisolone acetate 1% every 2 hours No
61F
(Shah et al., 2022)
N/A mRNA- 1273 (2) PK 14 Corneal stroma oedema, Khodadoust’s line Topical prednisolone acetate 1% hourly No
69F
(Shah et al., 2022)
N/A mRNA- 1273 (2) DSAEK 14 Corneal oedema Topical prednisolone acetate 1% and difluprednate 0.05% 6x per day No
77M
(Shah et al., 2022)
N/A mRNA- 1273 (2) PK 7 Corneal oedema, KPs AC
inflammation
Topical prednisolone acetate 1% 5x per day No
Review
(Dugan and Mian, 2022)
N/A N/A N/A N/A N/A N/A Risk factors for vaccination associated rejection include PK, repeat graft, infection, poor ocular surface and young age
566 episodes of corneal graft rejection from 2018 to 2021
across 2 centres (Roberts et al., 2022)
N/A N/A N/A N/A N/A N/A Median rates of rejection before and after initiation of vaccination program were not statistically different
Review
(Bizimungu C. et al., 2023)
N/A N/A N/A N/A N/A N/A Link between vaccine and rejection

Cases arranged by outcome and vaccine subtype.