Case Series Highlights Retinal manifestations associated with COVID 19 infection: IJO study
The corona virus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. Apart from severe systemic disease, various ophthalmic manifestations have been reported, ranging from anterior segment involvement such as conjunctivitis, severe keratitis and acute angle closure; retinal such as microangiopathy, cotton wool spots, hemorrhages and retinal vascular occlusions; and neuro‑ophthalmic manifestations including optic neuritis, extra‑ocular muscle palsies and idiopathic intracranial hypertension with papilledema.
These ophthalmological manifestations are attributed to: 1) a direct result of the viral infection and its cytopathological effects; 2) adverse effects of the pharmacological therapy administered for COVID‑19 infection; 3) manifestations related to prolonged hospitalization and intensive care (such as nosocomial infections) 4) and lastly due to alterations in the host immune response.
Goyal M, Murthy SI, Annum S reported a series of cases of retinal manifestations in patients associated with COVID‑19 infection, ranging from mild to vision threatening conditions published in Indian Journal of Ophthalmology.
This was a retrospective chart review wherein all consecutive cases presenting to the Retina‑Uveitis service from May 2020 to January 2021 with retinal manifestations associated with COVID‑19 infection or its sequelae or as a result of treatment given for COVID‑19 were included.
Of the 7 patients, 3 were female, and 4 were male. Four patients had onset of symptoms during the active phase of COVID‑19 infection. Four had bilateral and three had unilateral involvement. The manifestations ranged from mild to vision threatening.
Case 1: Presumed fungal endogenous endophthalmitis
A 46‑year‑old man presented with a 4‑week history of right eye (RE) ocular pain, redness and visual loss. He was diagnosed and treated for COVID‑19 infection two weeks before onset of symptoms. At presentation, visual acuity was hand motions; examination showed ciliary congestion, anterior chamber showed 2 + cells and 1 mm hypopyon and there were dense vitreous exudates. B‑scan revealed vitreous echoes and attached retina.
A diagnosis of endogenous endophthalmitis was made and he underwent pars plans vitrectomy with injection of intravitreal vancomycin 1.0 mg, amikacin 300 ug, amphotericin‑B 5 ug and voriconazole 100 ug. On table the vitreous exudates appeared dry with snowball like accumulations suggesting fungal infection. Thick sheets of pre‑retinal exudates were seen in the inferior periphery. Oral voriconazole was continued for 6 weeks. The infection resolved rapidly with visual recovery to 6/9 six weeks later.
Case 2: Candida retinitis
A 57‑year‑old male, diabetic and hypertensive, was hospitalized for severe Candida septicemia, with renal infection during COVID‑19 infection. Blood and urine cultures were positive for Candida tropicalis. The patient did not complain of loss of vision but on testing, his visual acuity had dropped to counting fingers at 2 meters in his RE. LE was normal. RE showed 2 + cells and flare and 1+ vitreous cells and three well‑circumscribed retinitis lesions in his RE, one involving the center of macula. He was switched from systemic fluconazole to intra‑venous voriconazole 200 mg twice daily due to the superior ocular bioavailability of the latter.
After two weeks, the retinitis appeared to be resolving but subsequently worsened. Intravitreal amphotericin‑B 5 ug and voriconazole 100 ug were given. Ten days later, there was increase in the vitreous haze, but the original retinitis lesions were resolving. As he was not systemically fit to undergo surgery, intervention was deferred and the ocular condition was closely monitored. Four weeks after the intravitreal injection, the vitreous inflammation persisted but retinitis showed early signs of resolution. Systemic voriconazole was continued for the renal and ocular infection and 3 months following the intravitreal injection his visual acuity improved to 6/36 with complete resolution of the vitreous inflammation and retinitis. He was advised to continue oral voriconazole for a further 4 weeks.
Case 3: Choroidal abscess
A 59‑year‑old lady presented with complaint of RE visual deterioration and nocturnal low‑grade fever for 4 weeks. Symptoms had started 2 months ago during COVID‑19 infection, for which systemic steroids were given for 4 weeks. On examination, visual acuity was 6/9 and 6/6 in the RE and LE respectively. LE was normal. RE showed 1 + vitreous cells and a large choroidal abscess supero‑temporal to the macula. The abscess showed central activity, scarring at its edges and multiple discrete yellow miliary lesions around it. OCT revealed vitreous traction over the lesion.
Based on the clinical appearance of the chorio‑retinal lesions, a provisional diagnosis of tuberculosis was considered. After discussion with her internist, a therapeutic trial of 4‑drug anti‑tubercular therapy (ATT) was started, with the intention of considering vitreous biopsy in case of worsening. She was closely followed up every week and the lesions showed improvement. Six‑weeks after initiating ATT the choroidal abscess and the miliary lesions had resolved significantly. The splenic abscesses had also started showing resolution. She was continued on 4‑drug ATT for the first two months with the intention to continue 2‑drug ATT for 10 months.
Case 4. Acute macular neuroretinopathy (AMN) and paracentral acute middle maculopathy (PAMM)
A 32‑year‑old man presented with 3‑day onset of paracentral and triangular negative scotoma in RE infero‑temporal visual field. He had recovered from COVID‑19 infection 4 months prior.
LE was asymptomatic. RE fundus revealed a triangular deeper retinal greyish‑white lesion located supero‑nasal to center of macula. OCT over the corresponding area showed disruption in the outer retinal layers, hyper‑reflective lesions in superficial retinal layers with shadowing of deeper retina. The entire inner retinal surface just inferior to foveal center showed hyper‑reflectivity. LE fundus revealed small greyish‑white lesion nasal to the foveal center and multiple similar lesions inferonasal and temporal to the cente
OCT revealed a single hyper‑reflective lesion in the superficial retina with underlying shadowing temporal to the center and hyper‑reflectivity of the entire inner retinal surface. Based on the characteristic symptoms, the fundus lesions and OCT findings he was diagnosed as post COVID‑19 RE symptomatic AMN, and bilateral asymptomatic PAMM. He was placed under observation.
Case 5: Central serous chorioretinopathy (CSCR)
A 27‑year‑old female patient presented with central vision deterioration in LE of 10‑days duration. She had recovered from COVID‑19 infection two weeks prior for which she had been on oral steroids. RE was normal; left eye visual acuity was 6/18. Examination showed no signs of inflammation. Fundus examination revealed serous detachment of the macula and was confirmed by OCT. She was observed and the symptoms resolved spontaneously a few weeks later.
Case 6: Post‑COVID‑19 sepsis related bilateral pre‑foveal hemorrhages
A 32‑year‑old lady in the ICU complained of rapid loss of central vision in both eyes (one month after COVID‑19 infection). She was admitted with fever and Pseudomonas sepsis while still on treatment for COVID‑19 infection.
Vision was counting fingers at 4 meters. Fundus examination showed bilateral pre‑foveal hemorrhages. Four weeks later she followed up in the outpatient department and reported no improvement. Her visual acuity was recorded as 6/18 in and 6/36 in the RE and LE respectively. Bilateral retinal hemorrhages were noted as before. The corresponding OCT showed pre‑foveal location with underlying shadowing.
A month later her visual acuity had improved to 6/6 and 6/9 in the RE and LE respectively. The pre‑foveal heme had resolved almost completely although the RE OCT showed residual paracentral pre‑foveal heme and the LE OCT now revealed some intraretinal heme.
Case 7: Voriconazole‑induced transient visual disturbance
A 40‑year‑old gentleman complained of multiple non‑specific but distressing visual symptoms including severe visual blur and extreme brightness and flashes of light for 3 weeks. He was admitted in ICU with invasive systemic aspergillosis and was on intravenous voriconazole (300 mg twice daily) for 4 weeks as microbiology isolates had shown sensitivity only to voriconazole.
The systemic aspergillosis had been diagnosed during his COVID‑19 infection, which he had developed 6 weeks prior. He was also on tablet augmentin 1 gram twice daily; oral mycophenolate mofetil 360 mg twice daily; oral prednisolone 5 mg daily; tacrolimus 0.5 mg twice daily; and subcutaneous insulin.
The BCVA was 6/6 BES. Color vision, pupil response to light, anterior segment and fundus evaluation were within normal limits in both eyes each eye. Perimetry was normal. A review of all the medications that the patient was on was done and based on the onset of his symptoms, a possibility of voriconazole‑induced visual symptoms was made. The dose of voriconazole was reduced with improvement in symptoms within a week. However, the drug had to be stepped up in view of his systemic condition of invasive aspergillosis and the patient again reported recurrence of his visual symptoms.
Authors described a series of cases with retinal manifestations, which were associated with COVID‑19 infection, with symptoms that started either during the infection or soon after resolution. Authors postulated that the severe infection in our otherwise healthy patient could be as a result of immunosuppression caused by COVID‑19 infection, and the steroids used for its management.
Study also had retinal manifestations due to the adverse effects of medication used for the management of COVID‑19 infection or its sequelae. CSCR is a recognized complication of steroid use and hence its association with COVID‑19 management is of course anticipated. However, there are no specific case reports of CSCR in patients with COVID‑19 infection.
Voriconazole is known to cause reversible visual symptoms in 18‑30% patients including altered light perception, photopsia, photophobia, blurred vision, or color vision changes but this often remains a diagnosis of exclusion. Considering the association of systemic fungal infections with COVID‑19 infection, voriconazole‑induced visual symptoms must remain as one of the possible causes of inexplicable visual symptoms in a setting of normal ocular examination in a COVID‑19 patient, as it is the easiest to reverse by simply decreasing or stopping the medication.
"While there are isolated case reports of COVID‑19 related retinal manifestations, this is the first single large case series of diverse retinal manifestations of COVID‑19 infection, some of these not reported, ranging from medication related mild adverse effects and post viral complications like PAMM and pre‑foveal hemorrhages to grave sight‑threatening ocular infections such as endophthalmitis, candida retinitis & tubercular choroidal abscess. Even in the severe cases, we could institute therapy promptly and our patients were able to recover well, suggesting an overall good prognosis in this subset of patients."
Source: Goyal M, Murthy SI, Annum S. Retinal manifestations in patients following COVID-19 infection: A consecutive case series. Indian J Ophthalmol 2021;69:1275-82.