In this study we analysed the OCTA and SD-OCT findings of recovered COVID-19 patients in early 3 months and compared to the control group.
The presence of the SARS-CoV-2 virus in tears of infected patients has been demonstrated, and the pathogen is known to cause ocular surface disorders, in different studies. [6,7,15] . Marinho et al were among the first to publish results suggesting retinal findings that could be associated with COVID-19. They reported nonspecific finding such as cotton wool spots, microhemorrhages. They also reported hyper-reflective changes in the inner retina that can be related to the COVID-19 . However a number of other authors have questioned these findings, raising the possibility that these hyper-reflective changes can be attributed to normal retinal structures, namely retinal blood vessels. [16-18] . Studies by Caporossi et al, Pereira et al, and Pirraglia et al included retinal examinations of patients with severe COVID-19, many of whom were at the time admitted in the intensive care unit. [19-21] While the first two groups reported evidence of microvascular disease such as retinal hemorrhages, cotton wool spots, retinal microaneurysms, and tortuous retinal vessels. Pirraglia et al did not see any of these changes in their cohort. It remains unclear if these microvascular changes can be attributed directly to COVID-19 or if they are a consequence of COVID-19 patients who needs intensive care unit, hemodynamic instability, increased inflammatory response. None of participants in our study were needed intensive care unit or positive pressure ventilation. The course of COVID- 19 was relatively mild with a none of patients requiring hospitalization in our study.
Abrishami et al reported decreased SFVD, DFVS, SPVD and DPVD on OCTA of patients with history of COVID-19 infection.  They analyzed the patients 2 weeks after recovery, we analyzed at least 4 to 12 weeks after recovery. Turker et al reported significantly lower SPVD in the the superior and nasal quadrants and also significantly lower DPVD in all quadrants of 6x6 mm macular images of OCTA in the COVID-19 patient group . The study group had significantly higher choriocapillaris flow area values and similar FAZ measurements. Their measurements were done within 1 week of discharge after complete recovery and the patient group all were hospitalized. Low oxygen saturation, severe lung involvement, impaired blood values such as high procalcitonin, D-dimer were among the indications for hospitalization. Within 1 week after discharged the findings in OCTA may be effected from the systemic situation. Therefore in this study we included the nonhospitalized mild COVID-19 patients. Differently from their study we analayzed the measurment of 3x3 mm macular images of OCTA in this study. Abrishami et al. reported decreased VD in SCP and DCP in an other study with the patients in a longitudinal midterm follow-up. They mentioned that changes were more pronounced in DCP.  In this study, we showed the SPVD was significantly lower in the COVID-19 patient group. DFVD, DPVS, SFVD were not significantly different between the groups.
Savastano et al identified reduced perfusion density of the PPCVD in recovered COVID-19 patients versus age-matched controls using OCTA analysis. The patient group they worked with was not homogeneous and consisted of participants who received various treatments like antiviral or anticuagulation or hydroxychloroquin and also had diseases such as diabetes and arterial hypertension, systemic autoimmune or inflammatory diseases. In this study PPCVD mean and related superior, inferior, nasal and temporal density components were all similar between the groups.
Abrishami et al found a trend towards increased retinal thickness in patients with history of COVID-19, though their comparison to age-matched controls did not reach statistical significance. Yıldız et al reported increased FMT but presence of comorbidities, including diabetes and hypertension, might have influenced retinal thickness measurements in their study. In this study we detected that FMT and PMT were not significantly different between the groups.
The choroid is the layer of the eye with the highest vascularization and also the tissue with the highest blood flow per unit weight in the body.  It also provides vascularization to the outer retina, the RPE, and some parts of the optic nerve and responsible for feeding the avascular fovea [28,29]. Hepokur et al reported that CT and total choroidal area were reduced in the early postinfectious period (15-40 days) of the disease and increased 9 months after the initial infection. . Fırat et al reported that there was no statistically significant difference between the groups in terms of FMT and CT in a period of 14-60 days after the onset of the first COVID-19 symptoms.  In this study we demonstrated significantly increased CT in COVID-19 patients group. The analyzed autopsy cohort of eyes from COVID-19 patients demonstrates an impairment of the microvessels mainly in the choroid. . Destruction of ACE2 receptors has been associated with multiorgan dysfunction owing to increased levels of reactive oxygen species, induction of fibrosis, hypertrophy, and inflammation. Therefore, decreased ACE2 expression in the neurosensory retinal cells and retinal vasculature could result in inflammation and oxidative stress, The increase in CT in the patient group was considered as a finding indicating that the inflammation continued even after 3 months.
In the present study we detected that InD VD was significantly decreased and superior PPRNFL was found to be significantly higher in the patient group. In a recently published case series, seven out of eight patients recovered from COVID-19 demonstrated an increase in PPRNFL thickness compared to their own available previous examinations. The only patient with decreased PPRNFL thickness had glaucoma.  Abrishami et al reported no significant difference in COVID-19 recovered patients at least a two week recovery period.  The measurements of the patient groups were taken at least 2 weeks after the recovery and it was not stated how long after the symptoms started or the PCR was positive, the measurements were taken. The fact that the patient group could not be analyzed within the same period may have affected the result. In this study İnD VD was significantly lower in the patient group. We think that the presence of microthrombus or endothelitis in microvascular structures that contribute to optic disc nutrition, similar to diseases such as glaucoma, optic neuropathy affecting the optic disc, cause this result.
The control group was consisting age and gender matched individuals. Ingrid Arevalo-Rodriguez et al reported the need for repeated testing in patients with suspicion of being infected because up to 54% of COVID-19 patients may have an initial negative RT-PCR result. They analysed information from 34 studies collecting information from 12,057 patients confirmed to have SARS-CoV-2 infection and 1060 cases with RT-PCR negative findings in their initial assessment. False-negative rates ranged from 0.018 to 0.58. Considering the possibility of including the participants that have unknowingly recovered from COVID-19 asymptomatically, without having PCR, or the recovered cases, who were not accepted as COVID-19 according to false negative PCR results although they showed symptoms and tested, we analaysed the data obtained before december 2019, the begining of pandemic COVID-19, as control group .As the superiority of our study, the patient group consists of individuals who are homogeneous, with similar periodic intervals in terms of disease onset and recovery time. The control group consists of healthy participants who are known to have not actually encountered the COVID- 19.
Limitations of our study; the small sample and the short and long-term measurements of the patients have not been compared.
In conclusion; In the present study, we evaluate COVID- 19 patients with OCT and OCT A. Microvascular changes occure in both the macula and optic disc. Also it seems that this vascular changes continue overtime. Large-scale studies are needed to guide the long-term follow-up of these patients.