Analyzing the effect of the COVID-19 pandemic on patient outcomes following keratorefractive surgery

Purpose : To evaluate the impact of the COVID-19 pandemic on keratorefractive surgery outcomes by comparing rates of post-operative complications prior to and during the pandemic. Methods : A retrospective cohort study was conducted using TriNetX (Cambridge, MA, USA), a federated electronic health records research network comprising multiple large health organizations in the United States. Patients were identified based on using validated CPT procedure codes for keratorefractive Surgery and were separated into two cohorts based on if they received their procedure before the pandemic protocols (Jan 1, 2019-Mar 17, 2020) or during the pandemic (Mar 18, 2020 to Dec 1, 2020). Then, 1:1 propensity score matching was utilized to create two same-sized cohorts which matched for various demographic and medical conditions. Subsequently, the relative risk for 11 specific post-operative complications between was compared between the two cohorts. Relative risks between cohorts were calculated and outcomes with p<0.05 were considered statistically significant. Results : A total of 2,626 patients were included in analysis with 1,313 in each of the prepandemic and pandemic cohorts after propensity matching. Dry eye had a greater risk (RR 1.29;95 Cl, 0.94, 1.77) among the pandemic cohort, however the results were not statically significant (P>0.113). Similarly, retinal detachment was observed to have a lower risk (RR 0.83;95% Cl, 0.36, 1.92) among the pandemic cohort but the results were not statistically significant either (P >0.663). No statistically significant differences in the remaining post-operative complications were observed including recurrent corneal erosion, secondary corneal erosion, corneal scar/opacity, diffuse lamellar keratitis, corneal neovascularization, vitreous degeneration and hemorrhage, retinal edema, and cystoid macular degeneration. Conclusions : The COVID-19 pandemic undoubtedly affected surgical practice of many ophthalmologists, and many operating rooms adopted new protocols after safety concerns for surgeons and ancillary staff. The results show that there was no statistically significant difference in the rate of post-operative complications for patients undergoing keratorefractive surgery before and during the pandemic. This suggests that despite the new safety protocols implemented in operating rooms, the quality-of-care patients received during the pandemic was not impacted.

Tissue-specific evidence for SARS-CoV-2 within intraocular tissues

Purpose : To systematically investigate ocular changes in autopsied eyes from fatal cases of Coronavirus disease 2019 (COVID-19) and to investigate the localization of severe acute respiratory syndrome coronavirus (SARS-CoV-2) within ocular structures. Methods : Macroscopic and microscopic histopathological evaluation was performed and the localization of SARS-CoV-2 RNA within ocular tissues investigated using an in situ hybridization (ISH) technique in 13 eyes. Contralateral eyes were freshly dissected, and droplet digital polymerase chain reaction (ddPCR) assay was performed on ocular fluids and tissues to quantify SARS-CoV-2 RNA. Results : A total of 21 fatal COVID-19 cases were included (mean age, 60.2 years [range, 27- 91 years];23.8% female). Histopathological abnormalities include vascular changes (61.9%), cytoid bodies (52.4%), and retinal edema (23.8%) with minimal inflammation (0.09%) were observed. Non-CMV viral inclusions were identified in one eye. No CMV positivity was detected. Of the 21 contralateral eyes tested by ddPCR, 14 tested positive for SARS-CoV-2. Using ddPCR and ISH, SARS-CoV-2 localization was observed in the following ocular tissues and fluid: cornea (27.3%), aqueous (26.3%), lens (54.5%), vitreous (15.0%), retina (22.2%), choroid/sclera (47.4%), and optic nerve (50.0%). The choroid/sclera, optic nerve and lens were the most frequent ocular structures found to be ddPCR positive. Evidence of replication was detected in four cases. Conclusions : Our results suggest that SARS-CoV-2 localizes to intraocular tissues. However, histological changes observed are likely a secondary hemodynamic change rather than primary effect of the virus.

A Cross-Sectional Study on the Effect of the COVID-19 Pandemic on Ocular Health at a Tertiary Care Department of Ophthalmology

Purpose : The COVID-19 pandemic caused disruptions in ophthalmic care, and may have negatively impacted some patients more than others. We performed a retrospective, cross-sectional study at our large, tertiary care ophthalmology referral center in the Midwest region of the United States in an attempt to identify patients at risk for worsening ocular health during the COVID-19 shutdowns. Methods : We completed retrospective Electronic Health Record data extraction of demographic and clinical outpatient encounter-level data for all patients examined in our department from March-May 2019, August-October 2019, March-May 2020 (peak COVID), and August-October 2020 (COVID recovery). Changes in mean logMAR visual acuity (logMAR VA), mean intraocular pressure (IOP), and mean number of procedures per encounter were tested and stratified by age (<18, 18-64, and 65+ years-old), and compared based on associated billing codes. Results : During peak COVID, there was a 73% decrease in the number of outpatient clinical encounters compared to the control time period in 2019 (6,976 vs. 26,068), and mean patient age was significantly lower during peak COVID (mean age 53.4, 95% CI 52.8- 54.0) compared with the other time periods. Documented best-corrected logMAR VA of the right and left eyes worsened for pediatric, adult, and elderly patient age groups;IOP of the right and left eyes worsened when evaluating all patients together;and the mean number of procedures performed per encounter increased by 74% comparing early 2019 to peak COVID months. The billing diagnoses associated with the worst ocular health outcomes during the COVID-related shutdowns include patients with anophthalmia of the fellow eye;infectious keratitis;open, chronic angle closure, and secondary causes of glaucoma;ocular inflammatory disorders;optic neuritis and ischemic optic neuropathies;and vitreoretinal disorders related to diabetes, macular degeneration, and vitreous or retinal hemorrhages. Conclusions : Patients seen during the COVID-19 pandemic were younger, had worsened logMAR VA, increased IOP, and underwent more procedures compared to the COVID-recovery and 2019 control months. Numerous billing diagnoses were associated with worse measures ocular health. Patients with these ocular disorders may need prioritization during future periods of reduced access ophthalmic care.

Retinas of human donors with COVID-19 disease show morphological alterations and signs of inflammation including glial activation

Purpose : Different signs of inflammation have been described in the brains of COVID-19 patients. In the retina, the fundus eye exam of these patients shows cotton wool spots, microhemorrhages, and a decrease in vascular density. However, morphological alterations of retinal cells in these patients are unknown. Thus, the aim was to analyze the morphological changes of the retinal cells from human donors with COVID-19 to establish several stages of response to damage in these cells and to define correlations with clinical parameters. Methods : The retinas of human donors with COVID-19 (n = 16) and control subjects (n = 12) obtained from the General University Hospital Consortium of Valencia were analyzed. Immunohistochemical stainings were performed on transversal sections or flat-mount retinas to study photoreceptors, microglial cells, Müller cells, astrocytes, and the presence of ACE2. TUNEL assays and confocal microscopy imaging were carried out. Correlations were calculated between retinal and clinical parameters. Results : Mean age of COVID-19 and control group were 80±10 and 70±8 years respectively. Müller cells, outer segment of cones and retinal pigment epithelium presented ACE2 staining. Larger staining of ACE2 and CRALBP was observed in cell bodies of Müller cells in COVID group. Disorganization of honeycomb-like pattern formed by Müller cells in the outer nuclear layer and disruption of external limiting membrane was found in the 81.3% of COVID patients. The 56.3% of COVID patients showed gliosis compared to controls (40%). COVID-19 retinas also presented epiretinal membranes and astrocytes protruding to vitreous humor. The 93.8% of COVID-19 patients had activated or ameboid-shape microglia. Microglial nodules around vessels and a reduction of the area occupied by microglia in these retinas were observed. COVID-19 group showed a more severe degeneration of cones. Cone degeneration correlated with Müller cell activation. Age of COVID patients correlated inversely with total retinal degeneration. Conclusions : Morphological alterations in the cone photoreceptors as well as glial activation showing an inflammatory state of the retina were observed in COVID-19 patients.

A UNIQUE CASE OF CANDIDA RETINITIS IN THE COVID-19 ERA

CASE: A 56-year-old male with a history of asthma was admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure. He was found to have sepsis secondary to pneumococcal pneumonia superinfected by COVID19. Labs showed elevated inflammatory markers. Chest x-ray initially demonstrated left lower lobe pneumonia but throughout the COVID-19 course, worsened to persistent multifocal pneumonia. The patient was intubated and treated with enoxaparin and a ten-day course of dexamethasone as well as antibiotics due to worsening clinical status. After the COVID-19 course resolved and the patient was extubated, he developed sepsis again - this time secondary to Candidemia. Treatment with intravenous micafungin was initiated and HIV antibodies screening returned negative. The patient began to report subacute visual changes including floating spots and blurry vision in the right eye without any other acute ocular symptoms. Upon ophthalmological exam, there were multiple white retinal lesions without vitreous involvement bilaterally on the macula indicating candida retinitis. Antifungal treatment with micafungin was changed to intravenous voriconazole for greater intraocular penetration. After seven days of intravenous voriconazole, two blood cultures came back negative for Candida. At this point, the patient was medically stable and was discharged on a six- week course of oral voriconazole. IMPACT/DISCUSSION: The COVID-19 pandemic changed the landscape of medicine. Not only have healthcare systems worked hard to treat the COVID-19 infections themselves but also the long-term effects that result from an infection. As treatment guidelines have been developed and honed, steroids appear at the forefront of therapy. However, this does not come without consequences as prolonged use of corticosteroids can dampen the body's immune system. This compounds the ability of COVID-19 pneumonia to result in a severely immunocompromised state that can subsequently expose the body to opportunistic infections. Candida albicans is an organism that exists in all humans in the gastrointestinal and genitourinary systems typically without impact. In severely immunocompromised individuals such as the patient in the case, hospital courses involving ICU care can lead to hematogenous spread of Candida. The candidemia leads to sepsis and may also present with rare clinical pictures such as Candida retinitis. For this reason, candidemia should prompt thorough evaluation of patients with an echocardiogram, abdominal computer tomography, and ophthalmologic exam. CONCLUSION: This case displays the ability of COVID-19 infections to provide an opportunity for rare infectious manifestations such as Candida retinitis. As the pandemic prolongs, proper treatment regimens must be reassessed for future use as these presentations may become more common.

Intravitreal C3F8 injection for the treatment of recalcitrant hypotony with suprachoroidal haemorrhage

Purpose: To describe a case of suprachoroidal haemorrhage and persistent hypotony successfully treated with intravitreal perfluoropropane (C3F8) and choroidal drainage. Methods: Case report and review of literature. Results: An 88 year-old male was referred with end-stage open angle glaucoma, recently complicated by idiopathic anterior uveitis and intraocular pressures of 39 mmHg and 41 mmHg in the right and left eyes respectively on maximal medical therapy. Visual acuity was count fingers in the right eye and 6/60 in the left. He underwent Baerveldt tube insertion in the left eye under local anaesthetic as COVID-19 precautions restricted general anaesthetic use. Unfortunately, he required increased sedation and post-operatively developed Type-1 respiratory failure and aspiration pneumonia with severe coughing. He was managed in intensive care. On discharge from hospital, he restarted antiglaucoma therapy against medical advice and developed a suprachoroidal haemorrhage with kissing choroidals. This failed to respond to medical therapy and anterior chamber reformation with viscoelastic substance. A choroidal drainage was performed, but the effusions recurred. Finally, a repeat choroidal drainage and injection of intravitreal 100% C3F8 stabilised the eye. After eleven months the right visual acuity was light perception, while the left visual acuity was 6/12 with an intraocular pressures of 11 mmHg on no medications. Conclusion: Intravitreal non-expansile gas injections have previously been described as a prophylactic measure for cases at high risk for suprachoroidal haemorrhage. To our knowledge, this is the first case of expansile C3F8 in the vitreous chamber used as rescue therapy for recalcitrant hypotony and suprachoroidal haemorrhage.

Occurrence of SARS-CoV-2 in the intraocular milieu.

The purpose of this research is to study the intraocular occurrence of SARS-CoV-2. In postmortem examinations, aqueous humor and the vitreous samples were collected. All individuals were previously positive in nasopharyngeal swabbing and cause of death was respiratory failure due to SARS-CoV-2 infection. Testing was done using quantitative RT-PCR. We included 16 aqueous humor and 16 vitreous samples for PCR testing. None of the results was positive for SARS-CoV-2. Human GAPDH genes to verify the presence of RNA was present in all aqueous humor samples (16/16, 100%) and 15/16 (93.8%) vitreous samples. In conclusion, this case series found no evidence of SARS-CoV-2 in the intraocular milieu.