Retinal Manifestations of COVID-19
The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis that is caused by the acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of March 12, 2022, there have been over 450 million confirmed cases of COVID-19 and over 6 million deaths around the world. Although most research and therapeutic efforts are directed toward the respiratory complications of the disease, COVID-19 can also lead to significant ophthalmic manifestations. The most commonly reported of these is conjunctivitis, which in some patients may be the only manifestation of SARS-CoV-2 infection. While eyelid, ocular surface, and anterior segment manifestations of COVID-19 are well documented, posterior segment involvement is less common and has mainly been described in the form of case reports. In this article, we will provide an overview of the most commonly reported retinal manifestations of COVID-19.
Retinal Manifestations of COVID-19
The most common retinal manifestations of COVID-19 are microvascular changes like cotton wool spots and retinal microhemorrhages. Many of these patients had preserved visual acuity and pupillary reflexes, but there have also been instances where patients developed visual field defects. The SARS-CoV-2 infection has also been associated with new-onset paracentral acute middle maculopathy (PAMM) and acute macular neuroretinopathy (AMN), although a true relationship between these conditions and COVID-19 is yet to be established. Increased tortuosity of retinal vessels is another finding that has been documented in patients with COVID-19. However, many of these retinal findings can also be seen in septic patients and patients with conditions like diabetic retinopathy, making it difficult to establish a true causal relationship between SARS-CoV-2 infection and microvascular retinal changes.
Retinal Vein Occlusion
Central Retinal Vein Occlusion (CRVO) has been identified as an important complication of COVID-19, as early detection and treatment are necessary for improved prognosis. SARS-CoV-2 infection is known to cause endothelial disruption, complement activation, and inflammation, leading to a hypercoagulable state that increases the risk of thrombus formation. Decreased vision and blurred vision are the most common presenting symptoms of CRVO and can start anytime from 5 days to 6 weeks after the initial onset of fever. Although CRVO is classically associated with risk factors like age, hypertension, glaucoma, and diabetes, COVID-19 may be associated with CRVO irrespective of patient age or comorbidities. Because timely diagnosis and management are crucial for vision preservation, clinicians should be vigilant about monitoring for signs of CRVO in patients with a history of COVID-19.
Retinal Artery Occlusion
Central retinal artery occlusion (CRAO) is a medical emergency that can lead to complete vision loss if not treated promptly and has also been documented in the context of SARS-CoV-2 infection. In case reports, patients developed sudden, unilateral, and painless vision loss two to six weeks after the initial onset of COVID-19 symptoms and were found to have mild-to-significant retinal whitening on fundus exam. However, it is important to note that most of these patients had additional underlying conditions like hypertension, obesity, and coronary artery disease, which may have placed them at a higher risk of developing CRAO. Regardless, because rapid identification and treatment are necessary to restore visual acuity, clinicians should consider CRAO in patients with a history of COVID-19 who present with sudden and painless vision loss.
Acute Macular neuroretinopathy
Acute Macular Neuroretinopathy is a rare condition marked by a wedge-shaped reddish-brown lesion reaching toward the fovea and resulting in a rapid onset of one or more paracentral scotomas. There are reports of a surge in the incidence of AMN during the COVID-19 pandemic. In some cases, AMN was detected as the first sign of COVID-19 infection who later developed fever and cough while testing positive for COVID-19. Etiology is unconfirmed. One theory is that microvascular ischemia of the choriocapillaris leads to hypoxic insult to the middle and outer retinal layers. This mechanism is particularly pertinent to recent reports of microthrombi found in patients with COVID-19.
Paracentral Acute Middle Maculopathy (PAMM)
Paracentral acute middle maculopathy (PAMM) is an optical coherence tomography (OCT) finding characterized by the parafoveal hyper‐reflective band at the level of the inner nuclear layer (INL). Although the exact etiopathogenesis of PAMM is not understood completely, ischemia of the retinal intermediate and deep capillary plexus has been shown to have a significant role. It is critical for physicians to recognize the signs and symptoms for an accurate diagnosis to ensure work‐up. Optical coherence tomography angiography shows perivascular hyper‐reflectivity and hyper‐reflective spots in the retinal deep capillary layer. 
Central serous chorioretinopathy (CSCR)
COVID-19 infection could be established as a risk factor for the development of CSCR, although the relationship remains ambiguous. A proposed mechanism can be mediated by the proven link between COVID-19 and the activation of the sympathetic system leading to choroidal leak and predisposing to CSCR. Such patients usually presented with a sudden blurring of vision in one eye, symptoms started 2 weeks to several months following COVID-19 infection. The diagnosis was confirmed using OCT. Most of the cases resolved spontaneously.
Fungal endogenous endophthalmitis (EE)
Various hypotheses have been put forward to the sudden surge of endogenous endophthalmitis cases in COVID-19 patients. Many of the patients had diabetes and required a high dose of systemic corticosteroid and/or further immunomodulation to combat the “cytokine storm.” Thus, a state of immunosuppression and the presence of systemic comorbidity were the prime suspects in such patients with EE. A decrease in the peripheral distribution of CD4+ T and CD8+ T cells has been reported in COVID-19 patients. Diagnosis of fungal EE requires a high index of suspicion. Irrespective of immune status, the ophthalmologist should investigate and explore the possibilities of dissemination of fungus in the bloodstream of patients with fungal EE. The contaminated intravenous fluid remains an important source of fungal EE in India. Microbiological investigation of the vitreous aspirates showed Aspergillus fumigatus, Aspergillus niger, Candida albicans, and Mucor. Timely diagnosis and management with intravitreal antifungals could salvage the eye in such patients.
Candida retinitis has been reported after COVID-19. Its diagnosis can be challenging in the initial stage with only chorioretinal involvement. Best-corrected visual acuity in such patients can be as bad as counting fingers close to face. Fundus examination may reveal clear vitreous, with multiple, yellowish-white, fluffy lesions, predominantly across the posterior pole. The foveal center can also be involved with the retinitis lesion. The diagnosis was confirmed by vitreous tap and blood culture. Intravitreal Voriconazole injection (100 micrograms in 0.1 ml) was given in most of the cases. Retinitis lesions and choroidals had regressed significantly and OCT showed regression of lesions. For this reason, candidemia should prompt a thorough evaluation of patients including an ophthalmologic exam.
While there are many case reports documenting retinal changes in the setting of COVID-19, the presence of additional comorbidities and their effects on the retina cannot be excluded. Despite this, clinicians should still be aware of and assess for the retinal manifestations of SARS-CoV-2 infection to prevent any vision-threatening complications. Future studies to investigate whether these documented retinal changes are truly attributable to COVID-19 or are incidental findings in the setting of clinical intercurrences are warranted.
- ↑ Cascella M, Rajnik M, Aleem A, et al. Features, Evaluation, and Treatment of Coronavirus (COVID-19) [Updated 2022 Oct 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/
- ↑ WHO Coronavirus (COVID-19) Dashboard. Accessed March 12, 2022. https://covid19.who.int
- ↑ Sen M, Honavar SG, Sharma N, Sachdev MS. COVID-19 and Eye: A Review of Ophthalmic Manifestations of COVID-19. Indian J Ophthalmol. 2021;69(3):488-509. doi:10.4103/ijo.IJO_297_21
- ↑ Bertoli F, Veritti D, Danese C, et al. Ocular Findings in COVID-19 Patients: A Review of Direct Manifestations and Indirect Effects on the Eye. J Ophthalmol. 2020;2020:4827304. doi:10.1155/2020/4827304
- ↑ Zhang Y, Stewart JM. Retinal and choroidal manifestations of COVID-19. Curr Opin Ophthalmol. 2021;32(6):536-540. doi:10.1097/ICU.0000000000000801
- ↑ Invernizzi A, Torre A, Parrulli S, et al. Retinal findings in patients with COVID-19: Results from the SERPICO-19 study. EClinicalMedicine. 2020;27:100550. doi:10.1016/j.eclinm.2020.100550
- ↑ Gonzalez-Lopez JJ, Felix Espinar B, Ye-Zhu C. Symptomatic Retinal Microangiopathy in a Patient with Coronavirus Disease 2019 (COVID-19): Single Case Report. Ocul Immunol Inflamm. 2021;29(4):642-644. doi:10.1080/09273948.2020.1852260
- ↑ Virgo J, Mohamed M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye. 2020;34(12):2352-2353. doi:10.1038/s41433-020-1069-8
- ↑ Hernandez M, González-Zamora J, Recalde S, et al. Evaluation of Macular Retinal Vessels and Histological Changes in Two Cases of COVID-19. Biomedicines. 2021;9(11):1546. doi:10.3390/biomedicines9111546
- ↑ Lani-Louzada R, Ramos C do VF, Cordeiro RM, Sadun AA. Retinal changes in COVID-19 hospitalized cases. PLoS One. 2020;15(12):e0243346. doi:10.1371/journal.pone.0243346
- ↑ Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management. Thromb Res. 2020;194:101-115. doi:10.1016/j.thromres.2020.06.029
- ↑ 12.0 12.1 Ullah I, Sohail A, Shah MUFA, et al. Central Retinal Vein Occlusion in patients with COVID-19 infection: A systematic review. Ann Med Surg (Lond). 2021;71:102898. doi:10.1016/j.amsu.2021.102898
- ↑ Ucar F, Cetinkaya S. Central retinal artery occlusion in a patient who contracted COVID-19 and review of similar cases. BMJ Case Reports CP. 2021;14(7):e244181. doi:10.1136/bcr-2021-244181
- ↑ Azar G, Bonnin S, Vasseur V, et al. Did the COVID-19 Pandemic Increase the Incidence of Acute Macular Neuroretinopathy?. J Clin Med. 2021;10(21):5038. Published 2021 Oct 28. doi:10.3390/jcm10215038
- ↑ Dehghani, A., Ghanbari, H., & Pourazizi, M. (2022). Paracentral acute middle maculopathy and COVID‐19 vaccination: Causation versus coincidence finding. Clinical Case Reports, 10(3). https://doi.org/10.1002/ccr3.5578
- ↑ Dutta Majumder P. Endogenous fungal endophthalmitis in COVID-19 patients: An unexplored possibility. Indian J Ophthalmol. 2022 Apr;70(4):1083-1085. doi: 10.4103/ijo.IJO_510_22. PMID: 35325989; PMCID: PMC9240571.
- ↑ Bhagali R, Prabhudesai NP, Prabhudesai MN. Post COVID-19 opportunistic candida retinitis: A case report. Indian J Ophthalmol. 2021 Apr;69(4):987-989. doi: 10.4103/ijo.IJO_3047_20. PMID: 33727474; PMCID: PMC8012955.