Retinal Findings in Hospitalized COVID-19 Patients, Is Routine Ophthalmological Examination Required after Discharge? Prospective Case-Control Study

Abstract

Objectives To investigate retinal findings by comparing patients hospitalized for COVID-19 with the control group.

Methods In this prospective study, 188 eyes of 94 recovered COVID-19 patients and 108 eyes of 54 healthy participants as a control group were evaluated. Patients were divided into three groups, those with mild, moderate, and severe COVID-19. Refractometry, tonometry, optical biometry, optical coherence tomography (OCT) measurements, and complete ophthalmological examinations were performed on healthy volunteers and COVID-19 patients on average 2 weeks after discharge. Pulse O₂ and vital parameters were also assessed. Primary outcomes were evaluated, such as retinal findings, and secondary outcomes as retinal thickness, choroidal thickness (CT), retinal nerve fiber layer thickness, and ganglion cell layer thickness.

Results There was no difference between the groups in terms of demographic data, ocular biometry, and intraocular pressure (p > 0.05). Pulse O₂ was lower in the study group (p < 0.001). Retinal findings were detected in 68 (36.1%) of 188 eyes in the study group and 28 (25.9%) of 108 eyes in the control group (p = 0.07). The two most common retinal findings were hypertensive retinopathy and retinal pigment epithelium alterations and/or drusen in both groups. In OCT measurements, significant thinning was observed in nasal macular thickness and superior 2 mm CT in the study group compared to the control group (p < 0.05). In patients divided into subgroups according to disease severity, no significant difference was found between the groups in any OCT parameter (p > 0.05).

Conclusion It has been observed that COVID-19 infection does not cause a specific and sensitive finding in the ocular tissues, especially the retina, and does not produce a reproducible measurement result. Recommending routine eye exam after COVID-19 does not seem cost-effective.

Zusammenfassung

Ziel Untersuchung der Netzhautbefunde durch Vergleich von Patienten, die wegen COVID-19 ins Krankenhaus eingeliefert wurden, mit der Kontrollgruppe.

Methode In dieser prospektiven Studie wurden 188 Augen von 94 genesenen COVID-19-Patienten und 108 Augen von 54 gesunden Teilnehmern als Kontrollgruppe ausgewertet. Die Patienten wurden in 3 Gruppen von leichtem, mittelschwerem und schwerem COVID-19 eingeteilt. Refraktometrie, Tonometrie, optische Biometrie, optische Kohärenztomografie-Messungen und vollständige ophthalmologische Untersuchungen wurden an gesunden Freiwilligen und Patienten im Durchschnitt 2 Wochen nach der Entlassung durchgeführt. Puls-O₂ und Vitalparameter wurden ebenfalls bewertet. Primäre Endpunkte wurden als Netzhautbefunde ausgewertet, sekundäre Endpunkte als Netzhautdicke, Aderhautdicke, Dicke der retinalen Nervenfaserschicht und Dicke der Ganglienzellschicht.

Ergebnisse Es gab keinen Unterschied zwischen den Gruppen in Bezug auf demografische Daten, Augenbiometrie und Augeninnendruck (p > 0,05). Der Puls-O₂ war in der Studiengruppe niedriger (p < 0,001). Netzhautbefunde wurden bei 68 (36,1%) von 188 Augen in der Studiengruppe und bei 28 (25,9%) von 108 Augen in der Kontrollgruppe festgestellt (p = 0,07). Bei der OCT-Messung wurde in der Studiengruppe im Vergleich zur Kontrollgruppe eine signifikante Ausdünnung der nasalen Makuladicke und der oberen Aderhautdicke von 2 mm beobachtet (p < 0.05). Es gab keinen signifikanten Unterschied zwischen Patienten mit und ohne Netzhautbefund (p > 0.05). Bei den Patienten, die nach Schweregrad der Erkrankung in Untergruppen eingeteilt wurden, wurde in keinem Parameter ein signifikanter Unterschied zwischen den Gruppen gefunden (p > 0,05).

Schlussfolgerung Es wurde beobachtet, dass eine COVID-19-Infektion keinen spezifischen und sensitiven Befund im Augengewebe, insbesondere der Netzhaut, hervorruft und kein reproduzierbares Messergebnis liefert. Eine routinemäßige Augenuntersuchung nach COVID-19 scheint nicht kosteneffektiv zu sein.

Key words

choroid - cotton wool spots - COVID-19 - OCT - retina

Schlüsselwörter

Aderhaut - Watteflecken - COVID-19 - OCT - Retina

Publication History

Received: 13 August 2022

Accepted: 09 October 2022

Article published online:
12 January 2023

• References

• 1 World Health Organization. WHO Coronavirus (COVID-19) Dashboard. Accessed November 08, 2022 at: https://covid19.who.int/
• 2 Ragab D, Salah Eldin H, Taeimah M. et al. The COVID-19 cytokine storm; what we know so far. Front Immunol 2020; 11: 1446
• 3 Levi M, Thachil J, Iba T. et al. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol 2020; 7: e438-e440
• 4 Gavriatopoulou M, Korompoki E, Fotiou D. et al. Organ-specific manifestations of COVID-19 infection. Clin Exp Med 2020; 20: 493-506
• 5 Ma D, Chen CB, Jhanji V. et al. Expression of SARS-CoV2 receptor ACE2 and TMPRSS2 in human primary conjunctival and pterygium cell lines and in mouse cornea. Eye (Lond) 2020; 34: 1212-1219
• 6 Senanayake Pd. Drazba J, Shadrach K. et al. Angiotensin II and its receptor subtypes in the human retina. Invest Ophthalmol Vis Sci 2007; 48: 3301-3311
• 7 Seah I, Agarwal R. Can the Coronavirus Disease 2019 (COVID-19) Affect the Eyes? A Review of Coronaviruses and Ocular Implications in Humans and Animals. Ocul Immunol Inflamm 2020; 28: 391-395
• 8 Rokohl AC, Grajewski RS, Matos PAW. et al. Ocular Involvement in COVID-19: Conjunctivitis and More. Klin Monbl Augenheilkd 2021; 238: 555-560
• 9 Ulhaq ZS, Soraya GV. The prevalence of ophthalmic manifestations in COVID-19 and the diagnostic value of ocular tissue/fluid. Graefes Arch Clin Exp Ophthalmol 2020; 258: 1351-1352
• 10 Marinho PM, Marcos AAA, Romano AC. et al. Retinal findings in patients with COVID-19. Lancet 2020; 395: 1610
• 11 Vavvas DG, Sarraf D, Sadda SR. et al. Concerns about the interpretation of OCT and fundus findings in COVID-19 patients in recent Lancet publication. Eye (Lond) 2020; 34: 2153-2154
• 12 Collison FT, Carroll J. Seeking clarity on retinal findings in patients with COVID-19. Lancet 2020; 396: e38
• 13 Landecho MF, Yuste JR, Gándara E. et al. COVID-19 retinal microangiopathy as an in vivo biomarker of systemic vascular disease?. J Intern Med 2021; 289: 116-120
• 14 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
• 15 Zapata MÁ, Banderas García S, Sánchez A. et al. Retinal microvascular abnormalities in patients after COVID-19 depending on disease severity. Br J Ophthalmol 2022; 106: 559-563
• 16 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
• 17 Gündogan M, Kiliç S, Göktas S. et al. Severe COVID-19 and Retina: Are There Any Retinal Manifestations?. Klin Monbl Augenheilkd 2022; 239: 284-287
• 18 Callaway E. Could new COVID variants undermine vaccines? Labs scramble to find out. Nature 2021; 589: 177-178
• 19 Republic of Turkey Ministry of Health Science Committee. COVID-19 Adult Patient Treatment Guide. Accessed November 08, 2022 at: https://covid19.saglik.gov.tr/Eklenti/43095/0/covid-19rehberieriskinhastayonetimivetedavi-12042022pdf.pdf
• 20 Turedi N, Onal Gunay B. Paracentral acute middle maculopathy in the setting of central retinal artery occlusion following COVID-19 diagnosis. Eur J Ophthalmol 2022; 32: NP62-NP66
• 21 Pereira LA, Soares LCM, Nascimento PA. et al. Retinal findings in hospitalised patients with severe COVID-19. Br J Ophthalmol 2020; 106: 102-105
• 22 Pirraglia MP, Ceccarelli G, Cerini A. et al. Retinal involvement and ocular findings in COVID-19 pneumonia patients. Sci Rep 2020; 10: 17419
• 23 Papazoglou A, Conen A, Haubitz S. et al. Ophthalmic Screening in Patients with Coronavirus Disease 2019: A Prospective Cohort Study. J Clin Med 2021; 10: 896
• 24 Sim R, Cheung G, Ting D. et al. Retinal microvascular signs in COVID-19. Br J Ophthalmol 2022; 106: 1308-1312
• 25 Zamora JG, Bilbao-Malavé V, Gándara E. et al. Retinal Microvascular Impairment in COVID-19 Bilateral Pneumonia Assessed by Optical Coherence Tomography Angiography. Biomedicines 2021; 9: 247
• 26 Savastano MC, Gambini G, Cozzupoli GM. et al. Retinal capillary involvement in early post-COVID-19 patients: a healthy controlled study. Graefes Arch Clin Exp Ophthalmol 2021; 259: 2157-2165
• 27 Aydemir E, Aydemir GA, Atesoglu HI. et al. The Impact of Coronavirus Disease 2019 (COVID-19) on Retinal Microcirculation in Human Subjects. Klin Monbl Augenheilkd 2021; 238: 1305-1311
• 28 Schachat AP, Wilkinson CP, Hinton DR, Sadda SR, Wiedemann P. eds. Ryanʼs Retina. 6th ed. Cleveland, OH, USA: Elsevier; 2018
• 29 Wong TY, Klein R, Klein BE. et al. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol 2001; 46: 59-80
• 30 Grosso A, Cheung N, Veglio F. et al. Similarities and differences in early retinal phenotypes in hypertension and diabetes. J Hypertens 2011; 29: 1667-1675
• 31 Sun L, Hymowitz M, Pomeranz HD. Eye Protection for Patients With COVID-19 Undergoing Prolonged Prone-Position Ventilation. JAMA Ophthalmol 2021; 139: 109-112
• 32 Giacuzzo C, Kawasaki A. Unilateral Optic Neuritis as the First and Only Manifestation of SARS-CoV-2 Infection. Klin Monbl Augenheilkd 2022; 239: 464-467
• 33 Karahan M, Erdem S, Hazar L. et al. Bilateral Central Retinal Artery Occlusion Secondary to SARS-CoV-2 Infection in the Early and Late Periods: A Case Report. Klin Monbl Augenheilkd 2021; 238: 1325-1327
• 34 Virgo J, Mohamed M. Paracentral acute middle maculopathy and acute macular neuroretinopathy following SARS-CoV-2 infection. Eye (Lond) 2020; 34: 2352-2353
• 35 Chirco KR, Potempa LA. C-reactive protein as a mediator of complement activation and ınflammatory signaling in age-related macular degeneration. Front Immunol 2018; 9: 539
• 36 Rohrer B, Frazer-Abel A, Leonard A. et al. Association of age-related macular degeneration with complement activation products, smoking, and single nucleotide polymorphisms in South Carolinians of European and African descent. Mol Vis 2019; 25: 79-92
• 37 Takase H, Kubono R, Terada Y. et al. Comparison of the ocular characteristics of anterior uveitis caused by herpes simplex virus, varicella-zoster virus, and cytomegalovirus. Jpn J Ophthalmol 2014; 58: 473-482