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.