Ocular Symptoms In COVID-19 Infection: A Survey Study.

Background: Coronavirus disease 2019 (COVID-19) systemic symptoms and sequelae have been studied extensively, but less is known about the characterization, duration, and long-term sequelae of ocular symptoms associated with COVID-19 infection. The purpose of this study was to analyze the frequency, spectrum, and duration of ocular symptoms in participants with COVID-19 infection treated in inpatient and outpatient settings. Methods: A retrospective electronic survey was distributed to NIH employees and the public who reported testing positive for SARS-CoV-2. The anonymous survey collected information on demographics, past ocular history, systemic COVID-19 symptoms, and ocular symptoms. Results: A total of 229 (21.9% male and 78.1% female, mean age 42.5 ±13.9) survey responses were included. Ocular symptoms were reported by 165 participants with a mean of 2.31±2.42 symptoms. The most commonly reported ocular symptoms were light sensitivity (31.0%), itchy eyes (24.9%), tearing (24.9%), eye redness (24.5%), and eye pain (24.5%). Participants with ocular symptoms had a higher number of systemic symptoms compared to participants without ocular symptoms (mean 9.17 ± 4.19 vs 6.22 ± 3.63; OR: 1.21; 95% CI: 1.11 - 1.32; p<0.001). Ocular symptoms were more common in those who reported a past ocular history compared to those who did not (81.8% vs 67.1%; OR: 2.17; 95% CI: 1.08 - 4.37; p=0.03). Additionally, the onset of ocular symptoms occurred most frequently at the same time as systemic symptoms (47.5%), and 12.6% reported symptoms lasting ≥14 days. Conclusions: Ocular surface-related symptoms are the most frequent ocular manifestations, and systemic disease severity is associated with the presence of ocular symptoms. Additionally, our results show that ocular symptoms can persist post-COVID-19 infection. Further work is needed to better understand ocular symptoms in COVID-19 and long-term sequelae.

Optical Coherence Tomography Angiography Changes in Choroidal Vasculature following Treatment in Punctate Inner Choroidopathy.

Purpose: To describe the changes seen on optical coherence tomography angiography [OCTA] in patients with PIC following immunosuppressive therapy.Methods: We reviewed serial OCTA scans from five consecutive PIC patients (5 eyes) with at least 3 months of follow-up, who underwent imaging before and after immunosuppressive therapy. Using ImageJ, superficial and deep retinal vasculature were analyzed for vessel area and foveal avascular zone. Choriocapillaris layer was analyzed for flow signal loss.Results: Five out of five patients received an orbital floor triamcinolone acetonide injection as the initial treatment for periods of activity. Mean choriocapillaris (CC) flow void area obtained after immunosuppressive therapy was significantly lower than the mean CC flow void area obtained prior to treatment (Pre-treatment: 0.270 vs Post-treatment: 0.144; p = .0068). In 2 out of 2 patients with longitudinal visual field testing, CC flow voids were spatially associated with visual field defects, and immunosuppressive therapy was associated with reduced CC flow void area and improved visual function.Conclusion: OCTA can detect alterations in choriocapillaris flow. Longitudinal follow-up demonstrates a centripetal restoration of choriocapillaris flow in response to immunosuppressive therapy. OCTA may be a useful adjunct for monitoring and evaluating treatment of PIC.

Gradient Boosted Decision Tree Classification of Endophthalmitis Versus Uveitis and Lymphoma from Aqueous and Vitreous IL-6 and IL-10 Levels.

PURPOSE: To investigate the effectiveness of gradient boosting to classify endophthalmitis versus uveitis and lymphoma by intraocular cytokine levels. METHOD: Patient diagnoses and aqueous and vitreous levels of interleukin (IL)-6 and IL-10 were retrospectively extracted from a National Eye Institute Histopathology Core database and compared by Kruskal-Wallis and post hoc Dunn tests. A gradient-boosted decision tree classifier was trained to differentiate endophthalmitis versus uveitis and lymphoma from vitreous IL-6 and IL-10, vitreous IL-6 only, and aqueous IL-6 only data sets; and was tested with 80-20 train-test split and 3-fold cross-validation of the training set. RESULTS: Seven endophthalmitis, 29 lymphoma, and 49 uveitis patients were included. IL-6 was higher in endophthalmitis than uveitis (P = 0.0713 aqueous, 0.0014 vitreous) and lymphoma (P = 0.0032 aqueous, 0.0001 vitreous). IL-10 was significantly higher in lymphoma than uveitis (P = 0.0017 aqueous, 0.0014 vitreous). Three-fold cross validation demonstrated 95% ± 5%, 95% ± 4%, and 97% ± 5% predictive accuracy for vitreous IL-6 and IL-10, vitreous IL-6 only, and aqueous IL-6 only data sets. Upon validation with the testing set, vitreous IL-6 and IL-10 and aqueous IL-6 only data sets achieved 100% predictive accuracy and vitreous IL-6 only data achieved 93% predictive accuracy with 100% sensitivity, 92% specificity, and an area under the receiver operating characteristic curve (ROC/AUC) of 96%. CONCLUSIONS: With limited sample size, gradient boosting can differentiate endophthalmitis from uveitis and lymphoma by IL-6 and IL-10 with high sensitivity and specificity; however, a larger cohort is needed for further validation.

Gender disparities in ocular inflammatory disorders.

Ocular inflammatory disorders disproportionately affect women, and the majority of affected women are of childbearing age. The role of sex or reproductive hormones has been proposed in many other inflammatory or autoimmune disorders, and findings from non-ocular autoimmune diseases suggest a complex interaction between sex hormones, genetic factors and the immune system. However, despite the age and sex bias, factors that influence this disparity are complicated and unclear. This review aims to evaluate the gender disparities in prevalence, incidence and severity of the most common infectious and non-infectious ocular inflammatory disorders.

Subclinical inflammation after laser in situ keratomileusis in corneal grafts.

PURPOSE: To evaluate postoperative inflammatory reaction in the eye after laser in situ keratomileusis (LASIK) in corneal grafts. SETTING: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland. METHODS: Ten eyes of 9 patients with penetrating keratoplasty (PKP) and significant postoperative refractive errors and astigmatism had LASIK 22 months or more after the PKP. All patients were treated with the VISX Star excimer laser and the Bausch & Lomb Hansatome microkeratome. Preoperative and early postoperative inflammation was evaluated by quantifying the aqueous flare intensity with a laser flare photometer (Kowa FM-500). A full ophthalmic assessment was also performed before LASIK and up to 6 months postoperatively. RESULTS: The inflammatory response was mild and limited to the first postoperative hour. The mean anterior chamber flare increased from 6.0 photons/millisecond (ph/ms) preoperatively to 14.0 ph/ms at 1 hour and then decreased to 6.7 ph/ms (hour 3), 6.8 ph/ms (day 1), and 8.2 ph/ms (day 7). The mean spherical equivalent (SE) refraction decreased from -3.81 diopters (D) (range -9.63 to -0.25 D) to -0.46 D (range -1.13 to +0.38 D), and the mean preoperative astigmatism decreased from 3.0 D (range 6.5 to 0.5 D) to 0.7 D (range 0.0 to 2.0 D). At the last examination, 9 eyes were within +/-1.0 D (6 within +/-0.5 D) and all were within +/-1.5 D of the intended SE refraction. Three eyes achieved full cylinder correction, and 7 were within +/-1.0 D of the intended correction. Eight eyes had a best corrected visual acuity of 20/40 or better (unchanged or gain of 1 to 4 lines [6], loss of 1 line [1], and loss of 3 lines [1]), and 8 had an uncorrected visual acuity of 20/50 or better. CONCLUSIONS: Uneventful LASIK induced subtle, short-lasting anterior chamber flare when measured by the laser flare meter. In corneal grafts, LASIK appeared to be a safe and effective procedure for residual refractive errors.

A rare case of endogenous Aspergillus conicus endophthalmitis in an immunocompromised patient.

BACKGROUND: The purpose of this study was to report the case of a patient with bilateral panuveitis who was found to have a rarely reported intraocular fungus, Aspergillus conicus. A 40-year-old man presented with gradual vision loss in both eyes. He had bilateral anterior uveitis, granulomatous vitritis with a preretinal granuloma in the right eye, and nongranulomatous vitritis with two quadrants of chorioretinal scarring in the left. FINDINGS: Serological testing revealed a new diagnosis of human immunodeficiency virus as well as positive rapid plasma reagin and fluorescent treponemal antibody. Polymerase chain reaction (PCR) testing of the aqueous humor from the right eye identified A. conicus. Due to the indolent course of the endogenous fungal infection, the patient was treated with prednisolone acetate 1% eye drops, oral voriconazole, and highly active antiretroviral therapy. More than 1 year later, his vision remained 20/20 in both eyes without any episodes of recurrent inflammation. CONCLUSIONS: PCR testing helped identify a rare intraocular infection in an immunocompromised patient. In this case, A. conicus behaved less aggressively than other species of Aspergillus implicated in intraocular infection.

Fundus autofluorescence imaging of the white dot syndromes.

OBJECTIVE: To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). METHODS: Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. RESULTS: Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P < .001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P < .001). CONCLUSIONS: Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs.

High-dose humanized anti-IL-2 receptor alpha antibody (daclizumab) for the treatment of active, non-infectious uveitis.

PURPOSE: This study was designed to provide preliminary data regarding the safety and efficacy of high-dose humanized anti-IL-2 receptor (daclizumab) therapy for the treatment of active intermediate, posterior or panuveitis. METHODS: Five patients were recruited into this non-randomized, prospective pilot study of high-dose intravenous induction daclizumab therapy given at doses of 8mg/kg at day 0 and 4mg/kg at day 14. Patients who did not meet a safety endpoint at the 3-week follow-up evaluation were given the option of continuing therapy with subcutaneous daclizumab at 2mg/kg every 4 weeks for 52 weeks. The primary outcome assessed was a two-step decrease in vitreous haze at day 21. Secondary outcomes evaluated included best-corrected visual acuity, retinal thickness as measured by optical coherence tomography, retinal vascular leakage assessed by fluorescein angiography, anterior chamber and vitreous cellular inflammation. RESULTS: Four male patients and one female patient were enrolled. Diagnoses included birdshot retinochoroidopathy (two patients), Vogt-Koyanagi-Harada's disease, bilateral idiopathic panuveitis and bilateral idiopathic intermediate uveitis. By the 4th week, four of five patients demonstrated a two-step decrease in vitreous haze. The other participant did not meet this criterion until week 20, but all five patients maintained stability in vitreous haze grade throughout their follow-up periods. At enrollment, mean visual acuity (10 eyes in 5 patients) was 69.2 ETDRS letters and following treatment was 78.2 letters (p<0.12). Anterior chamber cell, vitreous cell, and vitreous haze also improved in the majority of eyes. Adverse events were generally mild except for one episode of left-lower lobe pneumonia requiring hospitalization and treatment. CONCLUSION: This is the first demonstration that high-dose daclizumab can reduce inflammation in active uveitis. Daclizumab was well tolerated but there may be a potential increased risk of infection associated with immunosuppression. All five patients demonstrated a decrease in vitreous haze and measures of intraocular inflammation at final follow-up. The results of this small, non-randomized pilot study support the consideration of high-dose daclizumab therapy in cases of active posterior uveitis.

Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration.

Therapy for severe uveitis is frequently long-term immunosuppression using systemic corticosteroids and cytotoxic agents, but side effects make long-term therapy difficult. A long-term (>4 year) Phase I/II single armed interventional study using intravenous anti-IL-2 receptor alpha treatments (daclizumab) and a short-term Phase II study evaluating the use of a subcutaneous daclizumab formulation were conducted. Patients were tapered off their systemic immunosuppressive therapy and received daclizumab infusions or subcutaneous injections at intervals varying from 2 to 6 weeks. In the long-term study, seven of ten enrolled patients were tapered from their original immunosuppressive medications and maintained exclusively on repeated daclizumab infusions for control of their uveitis for over 4 years. No patient was permanently removed from therapy for an adverse event ascribed to the medication. The use of 6-week infusion intervals led to recurrence of uveitis, while 2- to 4-week intervals did not. Only one patient developed measurable anti-daclizumab antibodies but this disappeared when subcutaneous therapy was begun. In the short-term study, four of the five patients receiving the subcutaneous formulation met the study endpoints for success within the first 12 weeks. All five were successful by 26 weeks. These studies provide preliminary evidence that regularly administered long-term daclizumab therapy can be given in lieu of standard immunosuppression for years to treat severe uveitis and that subcutaneously administered daclizumab appeared to be a clinically viable treatment strategy. These studies suggest that anti-IL-2 receptor blockade could be useful in the treatment of Th1-mediated autoimmune conditions.