Table 1.
Primary studies included in the review*
| Author (s) | Country | Population/sample size | Inclusion criteria | Study design | Ocular symptoms |
|---|---|---|---|---|---|
| Xia et al. 9 | China | 30 patients Male: 70% Age: 54.50±14.17 years |
SARS-CoV-2-infected patients | Prospective interventional case series | Conjunctivitis in 1 patient (3%) with aqueous secretion |
| Cheema et al. 10 | Canada | A female aged 29 years | Not mentioned | Case report | Unilateral conjunctivitis, watery discharge then mucus discharge, and follicles Normal VA at the presentation and then declined owing to subepithelial infiltrates with overlying epithelial defects |
| Chen et al. 11 | China | A male aged 30 years | Not mentioned | Case report | Bilateral acute follicular conjunctivitis: moderate conjunctival injection, watery discharge, inferior palpebral follicles, tender palpable preauricular lymph nodes |
| Lan et al. 12 | China | 81 cases: Males: 40.7% Age: 41.69±18.6 years One of them was medical staff |
Confirmed COVID-19 patients | Prospective series of case studies | Conjunctivitis in 4% (3) patients who did not meet the typical features of viral conjunctivitis The time from the first symptom to the diagnosis was 3.33±1.15 days, and the ophthalmological consultation was carried out on the 25.67±1.53 days after diagnosis |
| Huang et al. 13 | China | 37 Chinese patients 12 severe cases, others were mild Age: 41-58 years |
Patients with laboratory-confirmed COVID-19 | Prospective cross-sectional study | Conjunctivitis in 3 cases (8%) only |
| Wu et al. 14 | China | 38 patients: Male: 65.8% Age: 65.8±16.6 years |
Patients with COVID-19 treated from February 9 to 15, 2020, at a hospital center | Retrospective case series | Ocular manifestations in 32% of the patients in the form of conjunctivitis |
| Zhang et al. 15 | China | 102 patients: Male: 47% Age: 57.63±14.90 years |
COVID-19 patients between December 30, 2019, and February 7, 2020 | Retrospective cross-sectional study | Bilateral conjunctivitis in 3% of 72 COVID-19 patients with watery discharges |
| Colavita et al. 16 | Italy | A 65-year-old female | Not mentioned | Case report | Bilateral conjunctivitis |
| Guan et al. 17 | China | 1099 patients from 552 hospitals Male: 58.1% Age: 47 years (35-58 years) Healthcare workers: 3.5% |
Confirmed COVID-19 patients, between December 11, 2019, and January 29, 2020 | Retrospective cohort | Conjunctivitis: in (0.8%): 4/1099 patients had severe COVID-19 and 5/1099 patients had non-severe disease |
| Marinho et al. 18 | Brazil | 12 adults Male: 50% 9 physicians 2 healthcare workers Age: 25-69 years |
SARS-CoV-2-infected patients | Case report | Retinal and OCT findings in the form of cotton wool spots and microhemorrhages along the retinal arcade in color fundus photograph (4 patients) Hyperreflective lesions at the level of ganglion cells and inner plexiform layers more prominently at the papillomacular bundle in both eyes Normal OCT-angiography |
| Leung et al. 19 | United States | 7 patients | Patients on hydroxychloroquine plus erlotinib therapy | Retrospective observational case series | 2 of 7 patients who received the high dose of HCQ developed macular abnormalities detected by retinal imaging and multifocal electroretinogram without visual symptoms |
| Chen et al.20 | China | 534 cases in China Male: 55.55% (conjunctivitis group) Age: 44 years (median) |
Patients were recruited from February 1 to March 1, 2020, not hospitalized, not severe cases, with smartphone and who accepted the questionnaire | Cross-sectional study | Conjunctivitis in 5% Hand-eye contact was independently correlated with conjunctivitis symptoms |
| Daruich et al.21 | Argentina | 27-year-old male | Not mentioned | Case report | Unilateral moderate conjunctivitis |
| Salducci and La Torre22 | Italy | An Italian patient: 72 years old with type 2 diabetes mellitus | Not mentioned | Case report | Bilateral conjunctivitis: serous secretions, conjunctival chemosis, and pseudomembranes on the tarsal conjunctiva |
| Karimi et al.23 | Iran | 43 patients: Male: 67.5% Age: 56±13 years (43-69 years) |
Clinically confirmed COVID-19 patients between March 28, 2020, and April 5, 2020 | Prospective case series | Bilateral conjunctivitis in 2.3% Mucus discharge, while another patient had bilateral foreign body sensation (2.3%) |
| Zhou et al.24 | China | 67 patients: majority were healthcare workers Male: 25 Age: 35.7±10.6 years |
Confirmed or suspected COVID-19 pneumonia during January 17-28, 2020 | Retrospective cohort study | Conjunctivitis |
| Sun et al.25 | China | 72 patients: Male: 50% Age: 58.68±14.81 years |
COVID-19 patients from December 30, 2019, to February 7, 2020, at Tongji Hospital | Single-center cross-sectional study | Bilateral conjunctivitis in 3% with watery discharges and without tenderness or enlargement of the preauricular lymph node |
| Navel et al.26 | France | A 63-year-old male | Not mentioned | Case report | Conjunctivitis was the first ocular manifestations Followed by follicles, tarsal hemorrhages, thin yellowish-white translucent pseudomembranes on the tarsal conjunctiva of lower lids, and superficial punctate keratitis |
| Deng et al.27 | China | 114 patients in China: Male: 54% Age: 61.4±16.7 years |
Patients with COVID-19 pneumonia recruited from February 3 to February 10, 2020, at Tongji Hospital | Observational study | No ocular complications or signs of ocular transmissible routes were reported |
| Zhang et al.28 | China | 14 confirmed, 16 suspected patients Age in the confirmed group: 48±13.4 years Age in the suspected group: 40±16.2 years |
All patients with diagnosed and suspected COVID-19 in Shenyang | Cross-sectional non-randomized study | Not mentioned |
| Xie et al.29 | China | 33 patients without ocular manifestation: Male: 66.7% Age: 57.6±14.0 years |
COVID-19 patients without any ocular manifestation from February 12 to 28, 2020 | Retrospective cohort study | SARS-CoV-2 might spread from normal conjunctiva of COVID-19 patients |
| Jun et al.30 | Singapore | 17 patients | SARS-COV-2-infected patients | Prospective study case series | Conjunctivitis in one patient |
| Dinkin et al. 31 | United States | 2 confirmed cases First case: a 36-year-old male Second case: a 71-year-old female |
Not mentioned | Case report | First case: a partial center oculomotor nerve palsy, bilateral abducens palsies, and bilateral distal leg paresthesias. The condition improved partially before discharge 3 days after admission Second case: right abducent (6th nerve) palsy, she presented with diplopia and defective abduction. The condition improved 2 weeks after discharge |
| Bostanci Ceran and Ozates32 | Turkey | 93 patients Male: 58.1% Age: 39.4±21.9 years |
Hospitalized and clinically confirmed COVID-19 patients between March 11 and April 30, 2020 | Cross-sectional study | 21.5% had at least one ocular manifestation: most common findings included hyperemia (20), epiphora (9), increased secretion (6), chemosis (3), follicular conjunctivitis (2), and episcleritis (2) The most common symptom was photophobia (15) |
| Abrishami et al. 33 | Iran | 142 patients Male: 54.2% Age: 62.6±15 years |
Consecutive patients with confirmed COVID-19 at the central referral center | Cross-sectional study | Ocular manifestations: in 65% patients Conjunctival hyperemia: 31%, conjunctival chemosis: 16%. Conjunctival chemosis was the most common ocular manifestation in ICU patients |
| Khavandi et al. 34 | Iran | A 65-year-old Caucasian diabetic male patient | Not mentioned | Letter to the editor | Follicular conjunctivitis with conjunctival chemosis and mucoid discharge |
| Nayak et al. 35 | India | A 65-year-old diabetic, hypertensive, and asthmatic patient on ventilator | Not mentioned | Case report | Unilateral severe follicular conjunctivitis Ocular signs without any complications |
| Ozturker36 | Turkey | A 32-year-old emergency healthcare worker | Not mentioned | Case report | Unilateral conjunctivitis and photophobia for 1 day |
| Scalinci and Trovato Battagliola37 | Italy | 5 confirmed cases 4 males: 41, 43, 65, 48 years One female: 37 years |
COVID-19-confirmed cases referred to their clinic | Case series | All showed only acute conjunctivitis: conjunctival hyperemia, epiphora, discharge, and photophobia |
| Méndez Mangana et al. 38 | Spain | A 31-year-old female | Not mentioned | Letter to the editor | Unilateral acute nodular episcleritis A slightly elevated nodule with hyperemia at the inferotemporal sector without or impaired VA |
| Gangaputra and Patel39 | United States | A total of 450 surveys 144 (32.0%) were positive COVID-19 |
Participants responded to the survey 1-4 weeks after receiving their COVID-19 test results (positive or negative) | Retrospective survey questionnaire | 47% of patients reported ocular symptoms Eye pain in 19%, photophobia in 14%, flashes or floaters in 12%, blurry vision in 11%, and red eyes in 10% 27% experiencing persistent eye symptoms despite recovery |
| Sindhuja et al. 40 | India | 127 mild COVID-19 patients Male: 88.98% Age: 38.8 years (5-73 years) |
Mild COVID-19-positive cases admitted between March 27 and April 19, 2020 | Retrospective cross-sectional study | 9% had ocular complaints (one case was excluded due to previous cataract surgery) 6% had conjunctivitis and conjunctival congestion |
| Guo et al. 41 | China | A 53-year-old male | Not mentioned | Case report | Unilateral viral conjunctivitis Relapsing bilateral keratoconjunctivitis 5 days after the complete relieve |
| Ying et al. 42 | Malaysia | A 54-year-old female | Not mentioned | Case report | Bilateral conjunctivitis lasting for 4 days |
| Pascual-Prieto et al. 43 | Spain | 8 cases of ophthalmoparesis | Not mentioned | Letter to the editor | D. 2 cases with unilateral 6th nerve palsy, one case of bilateral 6th nerve palsy, and one case of unilateral 4th nerve palsy E. One case of 4th nerve palsy: diagnosed only by clinical presentation C. 2 cases of unilateral 3rd nerve palsy and one case of unilateral 6th nerve palsy |
| Kumar et al. 44 | India | 45 patients Male: 78% Age: 31.26±12.8 years |
Confirmed COVID-19 cases with or without ocular symptoms | Case series | Not mentioned |
| Güemes-Villahoz et al. 45 | Spain | 36 patients (72 eyes) Male: 44% Age: 67.9 years |
Over the age of 18 years, positive RT?PCR test from nasopharyngeal swab, hospitalized because of COVID-19 and ability to give verbal consent | A cross-sectional study | 50% presented unilateral conjunctivitis and the other 50% were bilateral, 72% presented mild eye redness, 50% presented moderate secretions |
| Joob and Wiwanitkit46 | Thailand | 82 COVID-19 cases | Not mentioned | Letter to the editor | No patients had ocular manifestation The virus is a large virus and it is usually hard to secrete via exocrine gland |
| Atum et al. 47 | Turkey | 40 COVID-19 patients Male: 62.5% Age: 41.38±23.7 years |
Patients with positive PCR of nasopharyngeal and oropharyngeal swabs | Prospective interventional case series study | Conjunctivitis in 25% |
| Zhou et al. 48 | China | 121 patients Male: 44% Age: 8 years (22-89 years) Mild/moderate disease in 52% Severe disease in 48% |
COVID-19 patients from January 17 through February 16, 2020, in the Renmin Hospital | Case series study | Ocular symptoms in 6.6%, itching in 62.5%, redness in 37.5%, tearing in 37.5%, discharge in 25%, and foreign body sensation in 25%. 7 were severe cases and 1 was a mild/moderate case |
| Valente et al. 49 | Italy | 27 pediatric patients Male: 20 (74%) Age 84 months (8 days-210 months) |
Confirmed COVID-19 patients, hospitalized from March 16 to April 15, 2020 | Prospective observational case series study | Mild viral conjunctivitis in 15%. |
| Mungmungpuntipantip and Wiwanitkit50 | Thailand | 48 COVID-19 patients | SARS-COV-2-infected patients | Letter to the editor | No ocular manifestations in all patients examined in Thailand |
| Insausti-García et al. 51 | Spain | A 40-year-old White male patient | Not-mentioned | Case report | Unilateral papillophlebitis center persistent and painless decrease of the visual sensitivity, VA was 20/20 Severe inflammation of the ONH, retinal venous vasodilatation and tortuosity, cotton-wool spots, and moderate superficial hemorrhages in all four quadrants FA: venous staining, leakage, optic disc leakage, and late staining. No evidence of ischemia or peripheral vasculitis VF: a diffuse sensitivity decrease, a slight central scotoma, and a moderate increase in the blind spot OCT: papillary edema without macular edema. One week later: macular edema and VA decreased to 20/200 |
| Not mentioned | Not mentioned | Negative conjunctival swabs in patients without conjunctivitis | Antiviral drug | ||
| Started on the 3rd day of presentation while VA started to decline on the 6th day | Cervical lymphadenopathy | Not mentioned | Oral valacyclovir 500 mg and moxifloxacin eye drops | ||
| Started 13 days after illness onset, reduced on day 15, and resolved on day 19 | Not mentioned | Positive conjunctival swab 13 days after onset and lasted for 5 days Conjunctival specimens on days 13, 14, 17, and 19 showed decreasing levels of viral RNA |
Ribavirin eye drops | ||
| Ocular discomfort appeared on the 16.67±9.29 days after the diagnosis of COVID-19 | Not mentioned | Negative conjunctival PCR in both eyes of all 3 patients 78 patients with no ocular manifestations were not tested with PCR |
Not mentioned | ||
| Not mentioned | Not mentioned | Positive conjunctival swab in only one case of severe patients, but he had no conjunctivitis | Not mentioned | ||
| First symptom in 1 patient | Not mentioned | Positive nasopharyngeal PCR in 92% of ocular abnormality, positive conjunctival, and nasopharyngeal PCR in 17%, and positive conjunctival PCR in 5% | Not mentioned | ||
| Not mentioned | Not mentioned | Positive conjunctival swab of only one patient of the 2 patients with conjunctivitis | Ganciclovir eye drops | ||
| Started before fever and other symptoms, improved on day 15, and resolved on day 20 | Not mentioned | Ocular swabs: PCR was positive from the 3rd day up to day 21, with declining virus concentration The virus was still detected in ocular swabs days after it was no longer detectable in nasal ones |
Not mentioned | ||
| Not mentioned | Enlargement of lymph nodes in 0.2% patients | Not mentioned | Not mentioned | ||
| 11-33 days from the onset of COVID-19 symptoms | Not mentioned | Not mentioned | Not mentioned | ||
| Not mentioned | No risk factors | Not mentioned | Not mentioned | ||
| Conjunctivitis as initial symptom in 4 patients with a duration of 5.9±4.5 days/range 2-24 days | Not mentioned | Not mentioned | Ofloxacin, tobramycin, and ganciclovir eye drops | ||
| Conjunctivitis as the first presentation | Followed by severe respiratory symptoms | Not mentioned | A topical association of antibiotic and corticoids | ||
| Not-mentioned | Preauricular and submaxillary lymph nodes enlargement | Not mentioned | Cold compress, artificial tears, and topical ganciclovir 5 times/day for 7 days | ||
| Started 3 days before the onset of systemic manifestations | 95.3% had fever at the time of sampling | 7% of tear samples and 70% of nasopharyngeal samples were positive Positive tear RT-PCR in the patient with conjunctivitis but negative in the patient with ocular foreign body sensation All patients with positive tear RT-PCR had positive nasopharyngeal RT-PCR results |
Not mentioned | ||
| First symptom in one patient with a negative conjunctival swab | Not mentioned | 3 had positive conjunctival swab without ocular symptoms | Not mentioned | ||
| Not mentioned | Not mentioned | Positive conjunctival swab in one patient The time for sampling: 18.15±7.57 days |
Ganciclovir eye drops | ||
| Started on day 17 of illness and decreased from day 21 to day 26 | Not mentioned | On day 20, negative PCR of conjunctival scrapings and swabs for COVID-19 | Azithromycin eye drops twice/day for 3 days and dexamethasone with daily debridement of pseudomembranous | ||
| Not mentioned | Not mentioned | Negative PCR in conjunctival swabs of all patients | Not mentioned | ||
| Not mentioned | Not mentioned | All the conjunctival results of PCR-test were negative | Not mentioned | ||
| Not mentioned | Not mentioned | Strong positive results in both eyes of 2 out of the 33 (90-year-old female and 48-year-old male) | Not mentioned | ||
| Not mentioned | Not mentioned | Negative PCR in all tear samples (64 samples) collected over 3 weeks, suggesting that transmission through tears is low | Not mentioned | ||
| Not mentioned | Not mentioned | Not mentioned | Not mentioned | ||
| Not mentioned | Not mentioned | Not mentioned | Not mentioned | ||
| Ocular manifestations appeared after the systemic symptoms | Not mentioned | Not mentioned | Not mentioned | ||
| Not mentioned | Fever, dry cough, shortness of breath, and bilateral pneumonia appeared 2 days later | Not mentioned | Not mentioned | ||
| Symptoms had a late onset and resolved over 2 weeks | No data | Not mentioned | Not mentioned | ||
| Not mentioned | No other extraocular manifestations | Negative conjunctival swab but positive nasopharyngeal swab | Not mentioned | ||
| Not mentioned | No reported extraocular manifestations | Not mentioned | Moxifloxacin eye drops | ||
| Appeared 7 days after the systemic manifestations | Not mentioned | Not mentioned | Artificial tears and fluorometholone for 3 days, tapered over weeks | ||
| 20.6% showed ocular symptoms before systemic ones | Not mentioned | Not mentioned | Not mentioned | ||
| 45%: before systemic symptoms, 4 patients during the 1st week and one patient during the 3rd week | 55% developed systemic symptoms along with ocular manifestations | Not mentioned | Not mentioned | ||
| Started 10 days after the onset of disease and relieved 6 days after treatment | Not mentioned | Not mentioned | Glucocorticoids for 5 days | ||
| Not mentioned | No other systemic manifestation | Positive PCR | Not mentioned | ||
| C. Respiratory symptoms preceded diplopia by 2 weeks Respiratory symptoms preceded diplopia by 30 days |
Not mentioned | A. All had positive PCR B. No PCR was tested |
Not mentioned | ||
| Not mentioned | Not mentioned | 2% was positive for RT-PCR in the conjunctival swab | Not mentioned | ||
| The mean days since the disease onset until conjunctivitis manifestation: 8 days The mean duration of the conjunctivitis: 3 days |
Not mentioned | Positive conjunctival swab in 5.5%, only one of the 18 patients with conjunctivitis, and one patient without conjunctivitis | Not mentioned | ||
| Not mentioned | Not mentioned | Not mentioned | Not mentioned | ||
| Not mentioned | Not mentioned | Positive conjunctival swab in 7.5%, one case only had conjunctivitis | Not mentioned | ||
| Not mentioned | Not mentioned | Positive conjunctival swab in only one patient with ocular manifestations and two without manifestations, showed The positivity was not correlated significantly with the duration of disease |
Not mentioned | ||
| Resolution of conjunctivitis was after 3-5 days from onset | No mentioned | Positive conjunctival swab in one patient 2 patients were also positive but without conjunctivitis Swab became negative for all patients in 4 days |
Not mentioned | ||
| Not mentioned | Not mentioned | Not mentioned | Not mentioned | ||
| Appeared 6 weeks after the onset of the disease with gradual recovery of vision to 20/40 2 weeks later | Not mentioned | Not mentioned | Acetylsalicylic acid orally and bromfenac 0.9 mg/mL eye drops. Then sustained-release dexamethasone implant (Ozurdex, Allergan) |
*Primary studies: Means studies recording the primary study data. This is intended to answer scientific questions and to gain new knowledge. SARS-CoV-2: Severe acute respiratory syndrome coronavirus-2, VA: Visual acuity, COVID-19: Novel coronavirus 2019, RNA: Ribonucleic acid, PCR: Polymerase chain reaction, OCT: Optical coherence tomography, HCQ: Hydroxychloroquine, ICU: Intensive care unit, RT-PCR: Reverse transcription-PCR, ONH: Optic nerve head, FA: Fluorescein angiography, VF: Visual field