Showing papers in "JAMA Ophthalmology in 2021"
TL;DR: In this paper, the authors investigated the refractive changes and prevalence of myopia in school-aged children during the COVID-19 home confinement and found a substantial myopic shift (approximately −0.3 diopters [D]) was found in the 2020 school-based photoscreenings compared with previous years.
Abstract: Importance Time spent in outdoor activities has decreased owing to home confinement for the coronavirus disease 2019 (COVID-19) pandemic. Concerns have been raised about whether home confinement may have worsened the burden of myopia owing to substantially decreased time spent outdoors and increased screen time at home. Objective To investigate the refractive changes and prevalence of myopia in school-aged children during the COVID-19 home confinement. Design, Setting, and Participants A prospective cross-sectional study using school-based photoscreenings in 123 535 children aged 6 to 13 years from 10 elementary schools in Feicheng, China, was conducted. The study was performed during 6 consecutive years (2015-2020). Data were analyzed in July 2020. Exposures Noncycloplegic photorefraction was examined using a photoscreener device. Main Outcomes and Measures The spherical equivalent refraction was recorded for each child and the prevalence of myopia for each age group during each year was calculated. The mean spherical equivalent refraction and prevalence of myopia were compared between 2020 (after home confinement) and the previous 5 years for each age group. Results Of the 123 535 children included in the study, 64 335 (52.1%) were boys. A total of 194 904 test results (389 808 eyes) were included in the analysis. A substantial myopic shift (approximately −0.3 diopters [D]) was found in the 2020 school-based photoscreenings compared with previous years (2015-2019) for younger children aged 6 (−0.32 D), 7 (−0.28 D), and 8 (−0.29 D) years. The prevalence of myopia in the 2020 photoscreenings was higher than the highest prevalence of myopia within 2015-2019 for children aged 6 (21.5% vs 5.7%), 7 (26.2% vs 16.2%), and 8 (37.2% vs 27.7%) years. The differences in spherical equivalent refraction and the prevalence of myopia between 2020 and previous years were minimal in children aged 9 to 13 years. Conclusions and Relevance Home confinement during the COVID-19 pandemic appeared to be associated with a significant myopic shift for children aged 6 to 8 years according to 2020 school-based photoscreenings. However, numerous limitations warrant caution in the interpretation of these associations, including use of noncycloplegic refractions and lack of orthokeratology history or ocular biometry data. Younger children’s refractive status may be more sensitive to environmental changes than older ages, given the younger children are in a critical period for the development of myopia.
194 citations
TL;DR: In a case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design as discussed by the authors.
Abstract: Importance As vaccinations against COVID-19 continue, potential ocular adverse events should be reported in detail to increase awareness among the medical community, although typically, a causal relationship cannot be established definitively. Objective To describe ocular adverse events that occur soon after receiving an inactivated COVID-19 vaccination (Sinopharm). Design, setting, and participants This case series took place from September 2020 to January 2021 at Cleveland Clinic Abu Dhabi, a tertiary referral center. Patients who reported ocular adverse events and presented within 15 days from the first of 2 doses of an inactivated COVID-19 vaccine were analyzed. Main outcomes and measures Each patient underwent Snellen best-corrected visual acuity that was then converted to logMAR, applanation tonometry, and biomicroscopic examination with indirect ophthalmoscopy. Color fundus photography was obtained with a conventional 9-field fundus photography camera or with a widefield fundus photography system. Optical coherence tomography and optical coherence tomographic angiography images were obtained. Sex, race, age, and clinical data were self-reported. Results Nine eyes of 7 patients (3 male individuals) presenting with ocular complaints following COVID-19 vaccine were included in the study. The mean (SD) age was 41.4 (9.3) years (range, 30-55 years); the mean best-corrected visual acuity was 0.23 logMAR (range, 0-1 logMAR; approximate Snellen equivalent, 20/32). The mean time of ocular adverse event manifestations was 5.2 days (range, 1-10 days). One patient was diagnosed with episcleritis, 2 with anterior scleritis, 2 with acute macular neuroretinopathy, 1 with paracentral acute middle maculopathy, and 1 with subretinal fluid. Conclusions and relevance In this case series study of 7 patients, the timing of transient and ocular complications 5.2 days after vaccination with an inactivated COVID-19 vaccine supported an association with the ocular findings, but a causal relationship cannot be established from this study design.
89 citations
TL;DR: In this cross-sectional study, vision impairment and eye diseases were associated with lowerquality of life and more than half of the ophthalmic interventions included had a positive association with quality of life.
Abstract: Importance: More than 1 billion people worldwide have vision impairment or blindness from potentially preventable or correctable causes Quality of life, an important measure of physical, emotional, and social well-being, appears to be negatively associated with vision impairment, and increasingly, ophthalmic interventions are being assessed for their association with quality of life Objective: To examine the association between vision impairment or eye disease and quality of life, and the outcome of ophthalmic interventions on quality of life globally and across the life span, through an umbrella review or systematic review of systematic reviews Evidence Review: The electronic databases MEDLINE, Ovid, Embase, Cochrane Database of Systematic Reviews, Proquest Dissertations, and Theses Global were searched from inception through June 29, 2020, using a comprehensive search strategy Systematic reviews addressing vision impairment, eye disease, or ophthalmic interventions and quantitatively or qualitatively assessing health-related, vision-related, or disease-specific quality of life were included Article screening, quality appraisal, and data extraction were performed by 4 reviewers working independently and in duplicate The Joanna Briggs Institute critical appraisal and data extraction forms for umbrella reviews were used Findings: Nine systematic reviews evaluated the association between quality of life and vision impairment, age-related macular degeneration, glaucoma, diabetic retinopathy, or mendelian eye conditions (including retinitis pigmentosa) Of these, 5 were reviews of quantitative observational studies, 3 were reviews of qualitative studies, and 1 was a review of qualitative and quantitative studies All found an association between vision impairment and lower quality of life Sixty systematic reviews addressed at least 1 ophthalmic intervention in association with quality of life Overall, 33 unique interventions were investigated, of which 25 were found to improve quality of life compared with baseline measurements or a group receiving no intervention These interventions included timely cataract surgery, anti-vascular endothelial growth factor therapy for age-related macular degeneration, and macular edema Conclusions and Relevance: There is a consistent association between vision impairment, eye diseases, and reduced quality of life These findings support pursuing ophthalmic interventions, such as timely cataract surgery and anti-vascular endothelial growth factor therapy, for common retinal diseases, where indicated, to improve quality of life for millions of people globally each year
61 citations
TL;DR: In this article, the role of anti-vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy without center-involved diabetic macular edema (CI-DME) has not been clearly established.
Abstract: Importance The role of anti–vascular endothelial growth factor injections for the management of nonproliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) has not been clearly established. Objective To determine the efficacy of intravitreous aflibercept injections compared with sham treatment in preventing potentially vision-threatening complications in eyes with moderate to severe NPDR. Design, Setting, and Participants Data for this study were collected between January 15, 2016, and May 28, 2020, from the ongoing DRCR Retina Network Protocol W randomized clinical trial, conducted at 64 US and Canadian sites among 328 adults (399 eyes) with moderate to severe NPDR (Early Treatment Diabetic Retinopathy Study severity level, 43-53), without CI-DME. Analyses followed the intent-to-treat principle. Interventions Eyes were randomly assigned to 2.0 mg of aflibercept injections (n = 200) or sham (n = 199) given at baseline; 1, 2, and 4 months; and every 4 months through 2 years. Between 2 and 4 years, treatment was deferred if the eye had mild NPDR or better. Aflibercept was administered in both groups if CI-DME with vision loss (≥10 letters at 1 visit or 5-9 letters at 2 consecutive visits) or high-risk proliferative diabetic retinopathy (PDR) developed. Main Outcomes and Measures Development of CI-DME with vision loss or PDR through May 2020, when the last 2-year visit was completed. Results Among the 328 participants (57.6% men [230 of 399 eyes]; mean [SD] age, 56 [11] years), the 2-year cumulative probability of developing CI-DME with vision loss or PDR was 16.3% with aflibercept vs 43.5% with sham. The overall hazard ratio for either outcome was 0.32 (97.5% CI, 0.21-0.50;P Conclusions and Relevance In this randomized clinical trial, among eyes with moderate to severe NPDR, the proportion of eyes that developed PDR or vision-reducing CI-DME was lower with periodic aflibercept compared with sham treatment. However, through 2 years, preventive treatment did not confer visual acuity benefit compared with observation plus treatment with aflibercept only after development of PDR or vision-reducing CI-DME. The 4-year results will be important to assess longer-term visual acuity outcomes. Trial Registration ClinicalTrials.gov Identifier:NCT02634333
55 citations
TL;DR: In this paper, a cross-sectional study was conducted at the Duke Neurological Disorders Clinic in Durham, North Carolina to characterize alterations in the structure and microvasculature of the retina and choroid in individuals with Parkinson disease and compare them with eyes of age-and sex-matched cognitively healthy control individuals using OCT and OCT angiography.
Abstract: Importance Noninvasive retinal imaging may detect structural changes associated with Parkinson disease (PD) and may represent a novel biomarker for disease detection. Objective To characterize alterations in the structure and microvasculature of the retina and choroid in eyes of individuals with PD and compare them with eyes of age- and sex-matched cognitively healthy control individuals using optical coherence tomography (OCT) and OCT angiography (OCTA). Design, Setting, and Participants This cross-sectional study was conducted at the Duke Neurological Disorders Clinic in Durham, North Carolina. Individuals aged 50 years or older with a diagnosis of PD were eligible for inclusion and underwent an evaluation and diagnosis confirmation before enrollment. Control individuals aged 50 years or older and without subjective cognitive dysfunction, a history of tremor, or evidence of motor dysfunction consistent with parkinsonism were solicited from the clinic or the Duke Alzheimer’s Disease Prevention Registry. Individuals with diabetes, glaucoma, retinal pathology, other dementias, and corrected Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity worse than 20/40 Snellen were excluded. Data were analyzed between January 1, 2020, and March 30, 2020. Exposures All participants underwent OCT and OCTA imaging. Main Outcomes and Measures Generalized estimating equation analysis was used to characterize the association between imaging parameters and PD diagnosis. Superficial capillary plexus vessel density (VD) and perfusion density (PFD) were assessed within the ETDRS 6 × 6-mm circle, 6 × 6-mm inner ring, and 6 × 6-mm outer ring, as was the foveal avascular zone area. Peripapillary retinal nerve fiber layer thickness, macular ganglion cell–inner plexiform layer thickness, central subfield thickness, subfoveal choroidal thickness, total choroidal area, luminal area, and choroidal vascularity index (CVI) were measured. Results A total of 124 eyes of 69 participants with PD (39 men [56.5%]; mean [SD] age, 71.7 [7.0] years) and 248 eyes of 137 control participants (77 men [56.2%]; mean [SD] age, 70.9 [6.7] years) were analyzed. In the 6 × 6-mm ETDRS circle, VD (β coefficient = 0.37; 95% CI, 0.04-0.71;P = .03) and PFD (β coefficient = 0.009; 95% CI, 0.0003-0.018;P = .04) were lower in eyes of participants with PD. In the inner ring of the 6 × 6-mm ETDRS circle, VD (β coefficient = 0.61; 95% CI, 0.20-1.02;P = .003) and PFD (β coefficient = 0.015; 95% CI, 0.005-0.026;P = .004) were lower in eyes of participants with PD. Total choroidal area (β coefficient = –1.74 units2; 95% CI, −3.12 to −0.37 units2;P = .01) and luminal area (β coefficient = –1.02 units2; 95% CI, −1.86 to −0.18 units2;P = .02) were greater, but CVI was lower (β coefficient = 0.5%; 95% CI, 0.2%-0.8%;P Conclusions and Relevance This study found that individuals with PD had decreased retinal VD and PFD as well as choroidal structural changes compared with age- and sex-matched control participants. Given the observed population differences in these noninvasive retinal biomarkers, further research into their clinical utility in PD is needed.
54 citations
TL;DR: The PANORAMA study as mentioned in this paper evaluated vascular endothelial growth factor blockade therapy with intravitreal aflibercept injections in eyes with severe NPDR without diabetic macular edema (DME).
Abstract: Importance Proactive treatment of nonproliferative diabetic retinopathy (NPDR) reduces the risk of progression to vision-threatening complications. Objective To evaluate vascular endothelial growth factor blockade therapy with intravitreal aflibercept injections in eyes with severe NPDR without diabetic macular edema (DME). Design, Setting, and Participants The Study of the Efficacy and Safety of Intravitreal Aflibercept for the Improvement of Moderately Severe to Severe Nonproliferative Diabetic Retinopathy (PANORAMA) was a double-masked 100-week randomized clinical trial conducted in multiple centers worldwide. The study included 402 adults with Diabetic Retinopathy Severity Scale (DRSS) level 47 or 53 with no DME and best-corrected visual acuity of 20/40 or better. Interventions Intravitreal injections of aflibercept, 2 mg, every 16 weeks after 3 initial monthly doses and one 8-week interval (aflibercept 2q16 group); intravitreal injections of aflibercept, 2 mg, every 8 weeks after 5 initial monthly doses, with pro re nata (PRN) dosing beginning at week 56 (aflibercept 2q8/PRN group); or sham injections (control group). Main Outcomes and Measures Proportions of eyes with a 2-step or greater improvement in DRSS level, vision-threatening complications, and center-involved DME from baseline to weeks 24, 52, and 100. Results Among 402 participants (1 eye per participant), the mean (SD) age was 55.7 (10.5) years; 225 (56.0%) were male, and 310 (77.1%) were White. A total of 135 were randomized to the aflibercept 2q16 group, 134 to the aflibercept 2q8/PRN group, and 133 to the control group. At 24 weeks, treatment with aflibercept resulted in a 2-step or greater improvement in DRSS level in 157 of 269 eyes (58.4%) in the combined aflibercept groups vs 8 of 133 eyes (6.0%) in the control group (adjusted difference, 52.3%; 95% CI, 45.2%-59.5%; P < .001). At 52 weeks, 88 of 135 eyes (65.2%) in the aflibercept 2q16 group (adjusted difference, 50.1%; 95% CI, 40.1%-60.1%) and 107 of 134 eyes (79.9%) in the aflibercept 2q8/PRN group (adjusted difference, 64.8%; 95% CI, 55.8%-73.9%) compared with 20 of 133 eyes (15.0%) in the control group (P < .001 for both comparisons) showed a 2-step or greater improvement in DRSS level. Fewer eyes treated with aflibercept vs sham injections developed vision-threatening complications and/or center-involved DME through week 100 (22 of 135 eyes [16.3%] in the 2q16 group [adjusted difference, -34.2%; 95% CI, -44.6 to -23.8] and 25 of 134 eyes [18.7%] in the 2q8/PRN group [adjusted difference, -31.7%; 95% CI, -42.5 to -20.9] compared with 67 of 133 eyes [50.4%] in the control group; P < .001 for both comparisons). No new safety signals were identified. Conclusions and Relevance In this study, significantly more eyes with moderately severe to severe NPDR that were treated with aflibercept showed a 2-step or greater improvement in DRSS level at 24, 52, and 100 weeks, and significantly fewer eyes treated with aflibercept vs sham developed vision-threatening complications and center-involved DME. Outcomes on the DRSS between year 1 and 2 emphasize the need for ongoing vascular endothelial growth factor suppression and adherence. Trial Registration ClinicalTrials.gov Identifier: NCT02718326.
52 citations
TL;DR: In this paper, two groups of students from 12 primary schools in Guangzhou, China, were prospectively enrolled and monitored from grade 2 to grade 3, and the exposure and nonexposure groups were made to evaluate any association between environmental changes during the COVID-19 outbreak period and development of myopia.
Abstract: Importance: During the outbreak of COVID-19, outdoor activities were limited and digital learning increased. Concerns have arisen regarding the impact of these environmental changes on the development of myopia. Objective: To investigate changes in the development of myopia in young Chinese schoolchildren during the outbreak of COVID-19. Design, Setting, and Participants: In this observational study, 2 groups of students from 12 primary schools in Guangzhou, China, were prospectively enrolled and monitored from grade 2 to grade 3. Comparisons between the exposure and nonexposure groups were made to evaluate any association between environmental changes during the COVID-19 outbreak period and development of myopia. The exposure group received complete eye examinations in November and December 2019 and November and December 2020. The nonexposure group received examinations in November and December 2018 and November and December 2019. Main Outcomes and Measures: Changes in cycloplegic spherical equivalent refraction (SER), axial length (AL) elongation, and myopia incidence from grade 2 to grade 3. Results: Among the 2679 eligible students in grade 2 (mean [SD] age, 7.76 [0.32] years; 1422 [53.1%] male), 2114 (1060 in the nonexposure group and 1054 in the exposure group) were reexamined in grade 3. Compared with the period from November and December 2018 to November and December 2019, the shift of SER, AL elongation, and myopia incidence from grade 2 to grade 3 from November and December 2019 to November and December 2020 was 0.36 D greater (95% CI, 0.32-0.41; P < .001), 0.08 mm faster (95% CI, 0.06-0.10; P < .001), and 7.9% higher (95% CI, 5.1%-10.6%; P < .001), respectively. In grade 3 students, the prevalence of myopia increased from 13.3% (141 of 1060 students) in November and December 2019 to 20.8% (219 of 1054 students) in November and December 2020 (difference [95% CI], 7.5% [4.3-10.7]; P < .001); the proportion of children without myopia and with SER greater than -0.50 D and less than or equal to +0.50 D increased from 31.1% (286 of 919 students) to 49.0% (409 of 835 students) (difference [95% CI], 17.9% [13.3-22.4]; P < .001). Conclusions and Relevance: In this study, development of myopia increased during the COVID-19 outbreak period in young schoolchildren in China. Consequently, myopia prevalence and the proportion of children without myopia who were at risk of developing myopia increased. Future studies are needed to investigate long-term changes in myopia development after the COVID-19 pandemic.
49 citations
TL;DR: In this paper, the presence of SARS-CoV-2 RNA in corneal discs of deceased patients with confirmed COVID-19 and assess viral genomic and subgenomic RNA load, possible infectivity, and histologic abnormalities.
Abstract: Importance Current recommendations are to avoid tissue for corneal transplant from donors with coronavirus disease 2019 (COVID-19) or those who were recently exposed to COVID-19 owing to the lack of knowledge about the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in corneal tissues. Evidence of SARS-CoV-2 in corneal tissue would seem to have clinical relevance for corneal transplant. Objectives To investigate the presence of viral SARS-CoV-2 RNA in corneal discs of deceased patients with confirmed COVID-19 and assess viral genomic and subgenomic RNA load, possible infectivity, and histologic abnormalities. Design, Setting, and Participants A case series was conducted of 11 deceased patients with COVID-19 who underwent autopsy between March 20 and May 14, 2020. Eleven corneal discs (1 corneal disc per patient) were harvested for molecular detection of viral genomic and subgenomic RNA, virus isolation, and immunohistochemistry. The SARS-CoV-2 RNA loads were compared with RNA loads in the conjunctival and throat swab samples and aqueous humor, vitreous humor, and blood samples. Main Outcomes and Measures Evidence of SARS-CoV-2 RNA in human corneas. Results This study comprised 11 patients (6 women [55%]; mean [SD] age, 68.5 [18.8] years). In 6 of 11 eyes (55%), SARS-CoV-2 genomic RNA was detected in the cornea; subgenomic RNA was present in 4 of these 6 eyes (67%). Infectivity or the presence of viral structural proteins could not be confirmed in any eye. However, patients whose corneal disc was positive for SARS-CoV-2 RNA also had positive results for SARS-CoV-2 RNA in 4 of 6 conjunctival swab samples, 1 of 3 aqueous humor samples, 3 of 5 vitreous humor samples, and 4 of 5 blood samples. Overall, conjunctival swab samples had positive results for SARS-CoV-2 RNA in 5 of 11 cases. Postmortem SARS-CoV-2 viremia was detected in 5 of 9 patients. Conclusions and Relevance Viral genomic and subgenomic RNA of SARS-CoV-2 was detected in the cornea of patients with COVID-19 viremia. The risk of COVID-19 infection via corneal transplant is low even in donors with SARS-CoV-2 viremia, but further research is necessary to assess the rate of SARS-CoV-2 transmission via corneal transplant.
48 citations
TL;DR: In this article, the authors evaluated the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment.
Abstract: Importance Limited data exist on the real-world safety outcomes of patients with neovascular age-related macular degeneration treated with brolucizumab (Beovu). Objective To determine the real-world incidence of intraocular inflammation (IOI), including retinal vasculitis (RV) and/or retinal vascular occlusion (RO), for patients with neovascular age-related macular degeneration who underwent brolucizumab treatment. Additionally, potential risk factors associated with these adverse events were evaluated. Design, setting, and participants This cohort study included patients with neovascular age-related macular degeneration in the Intelligent Research in Sight (IRIS) Registry and Komodo Healthcare Map. Patients initiating and receiving 1 or more brolucizumab injections from October 8, 2019, to June 5, 2020, with up to 6 months of follow-up were included. Intervention Brolucizumab injections. Main outcome and measures Incidence of IOI (including RV) and/or RO and RV and/or RO and risk stratification for the identified risk factors. Results Of 10 654 and 11 161 included eyes (from the IRIS Registry and Komodo Health database, respectively), the median follow-up times were 97 and 95 days. Most eyes switched from another anti-vascular endothelial growth factor agent (9686 of 10 654 [90.9%] and 10 487 of 11 161 [94.0%], respectively), most commonly aflibercept (7160 of 9686 [73.9%] and 7156 of 10 487 [68.2%]), and most were from women (6105 of 10 654 [57.3%] and 6452 of 11 161 [57.8%]). The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively. Patients with a history of IOI and/or RO in the 12 months before brolucizumab initiation had an increased observed risk rate (8.7% [95% CI, 6.0%-11.4%] and 10.6% [95% CI, 7.5%-13.7%]) for an IOI and/or RO event in the 6 months following the first brolucizumab treatment compared with patients without prior IOI and/or RO (2.0% in both data sets). There was an increased estimated incidence rate in women (2.9% [95% CI, 2.5%-3.3%] and 3.0% [95% CI, 2.6%-3.4%]) compared with men (1.3% [95% CI, 1.0%-1.7%] and 1.4% [95% CI, 1.0%-1.7%]), but this risk was not as large as that of a prior IOI and/or RO. Similar findings were observed for patients with RV and/or RO events. Conclusions and relevance The incidence rate of IOI and/or RO was approximately 2.4%. Patient eyes with IOI and/or RO in the 12 months prior to first brolucizumab injection had the highest observed risk rate for IOI and/or RO in the early months after the first brolucizumab treatment. However, given study limitations, the identified risk factors cannot be used as predictors of IOI and/or RO events, and causality with brolucizumab cannot be assessed.
48 citations
TL;DR: In this article, a conjunctival swab was performed in 91 patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptasepolymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions.
Abstract: Importance Since February 2020, coronavirus disease 2019 (COVID-19) has spread rapidly all over the world, with an epidemiological cluster in Lombardy, Italy. The viral communicability may be mediated by various body fluids, but insufficient information is available on the presence of the virus in human tears. Objectives To investigate the rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears collected from patients with COVID-19 by means of real-time reverse transcriptase–polymerase chain reaction (rRT-PCR) assay and to assess the association of virus presence with concomitant clinical conditions. Design, Setting, and Participants Cross-sectional study conducted between April 9 and May 5, 2020. The setting was intensive care units at Azienda Socio-Sanitaria Territoriale (ASST) Sette-Laghi Hospital, University of Insubria, in Varese, Lombardy, Italy. A conjunctival swab was performed in 91 patients hospitalized for COVID-19, which was clinically diagnosed by rRT-PCR assay on nasopharyngeal swabs and by radiological imaging. Conjunctival swabs from 17 additional healthy volunteer participants with no symptoms of COVID-19 were examined to evaluate the availability and applicability of the conjunctival swab test. Exposure SARS-CoV-2 detection by means of rRT-PCR assay performed on the collected samples obtained by conjunctival swabs. Main Outcomes and Measures Conjunctival swab and nasopharyngeal swab results are reported, as well as demographic and clinical data. Results A total of 108 participants (mean [SD] age, 58.7 [14.2] years; 55 female and 53 male) were tested for SARS-CoV-2 using rRT-PCR assay, including 91 patients hospitalized with COVID-19 and 17 were healthy volunteers. SARS-CoV-2 was found on the ocular surface in 52 of 91 patients with COVID-19 (57.1%; 95% CI, 46.3%-67.5%), with a wide variability in the mean viral load from both eyes. Among a subset of 41 patients, concordance of 63.0% (95% CI, 41.0%-81.0%) was found between positive conjunctival and nasopharyngeal swab test results when performed within 2 days of each other. In 17 of these patients, nasopharyngeal swab results were negative for SARS-CoV-2. In 10 of these 17 patients, conjunctival swab results were positive for the virus. Conclusions and Relevance In this study, SARS-CoV-2 RNA was found on the ocular surface in a large part of this cohort of patients with COVID-19, although the infectivity of this material could not be determined. Because patients may have positive test results with a conjunctival swab and negative results with a nasopharyngeal swab, use of the slightly invasive conjunctival swab may be considered as a supplementary diagnostic test.
45 citations
TL;DR: In this article, a case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients with newly diagnosed age-related macular degeneration (AMD) from January 2008 to December 2017 were defined as cases and matched with control participants.
Abstract: Importance Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD. Objective To determine whether metformin use is associated with reduced odds of developing AMD. Design, setting, and participants This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020. Exposures Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims. Main outcomes and measures Risk of developing AMD. Results A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]). Conclusion and relevance In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.
TL;DR: In this article, the authors report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for neovascular age-related macular degeneration (nAMD).
Abstract: Importance Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti–vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). Objective To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. Design, Setting, and Participants This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. Exposures Treatment with brolucizumab IVI, 6 mg. Main Outcomes and Measures Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. Results A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, −2.7 to 4.3;P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm;P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. Conclusions and Relevance In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.
TL;DR: This randomized clinical equivalence trial found that SB11 demonstrated equivalence in efficacy for both primary end points: adjusted treatment differences between groups were within predefined equivalence margins.
Abstract: Importance Neovascular age-related macular degeneration is the leading cause of blindness in individuals 50 years or older. The availability of a ranibizumab biosimilar product (SB11) may facilitate access to an effective alternative to this treatment. Objective To demonstrate equivalence of efficacy, similar safety, and similar immunogenicity of SB11 compared with the reference ranibizumab. Design, Setting, and Participants This randomized, double-masked, parallel-group phase 3 equivalence study was conducted in 75 centers in 9 countries from March 14, 2018, to December 9, 2019, among 705 participants 50 years or older with neovascular age-related macular degeneration with active subfoveal choroidal neovascularization lesions. Analysis was performed on an intent-to-treat basis. Interventions Intravitreous injection of SB11 or ranibizumab, 0.5 mg, every 4 weeks through week 48. Main Outcomes and Measures Preplanned interim analysis after all participants completed the week 24 assessment of primary efficacy end points at week 8 for change from baseline in best-corrected visual acuity (BCVA) and week 4 for central subfield thickness (CST), with predefined equivalence margins for adjusted treatment differences of −3 letters to 3 letters for BCVA and −36 μm to 36 μm for CST. Results Baseline and disease characteristics among 705 randomized participants (403 women [57.2%]; mean [SD] age, 74.1 [8.5] years) were comparable between treatment groups (SB11, 351; ranibizumab, 354). Least-squares mean (SE) changes in BCVA from baseline at week 8 were 6.2 (0.5) letters in the SB11 group vs 7.0 (0.5) letters in the ranibizumab group, with an adjusted treatment difference of −0.8 letter (90% CI, −1.8 to 0.2 letters). Least-squares mean (SE) changes in CST from baseline at week 4 were −108 (5) μm in the SB11 group vs −100 (5) μm in the ranibizumab group, with an adjusted treatment difference of −8 μm (95% CI, −19 to 3 μm). Incidences of treatment-emergent adverse events (231 of 350 [66.0%] vs 237 of 354 [66.9%]), including serious treatment-emergent adverse events (44 of 350 [12.6%] vs 44 of 354 [12.4%]) and treatment-emergent adverse events leading to study drug discontinuation (8 of 350 [2.3%] vs 5 of 354 [1.4%]), were similar in the SB11 and ranibizumab groups. Immunogenicity was low, with a cumulative incidence of antidrug antibodies up to week 24 of 3.0% (10 of 330) in the SB11 group and 3.1% (10 of 327) in the ranibizumab group. Conclusions and Relevance These findings of equivalent efficacy and similar safety and immunogenicity profiles compared with ranibizumab support the use of SB11 for patients with neovascular age-related macular degeneration. Trial Registration ClinicalTrials.gov Identifier:NCT03150589
TL;DR: In this article, the prevalence of visual acuity loss and blindness by age, sex, race/ethnicity, and US state was estimated, stratified when possible by factors including US state, age group, sex and ethnicity.
Abstract: Importance Globally, more than 250 million people live with visual acuity loss or blindness, and people in the US fear losing vision more than memory, hearing, or speech. But it appears there are no recent empirical estimates of visual acuity loss or blindness for the US. Objective To produce estimates of visual acuity loss and blindness by age, sex, race/ethnicity, and US state. Data Sources Data from the American Community Survey (2017), National Health and Nutrition Examination Survey (1999-2008), and National Survey of Children’s Health (2017), as well as population-based studies (2000-2013), were included. Study Selection All relevant data from the US Centers for Disease Control and Prevention’s Vision and Eye Health Surveillance System were included. Data Extraction and Synthesis The prevalence of visual acuity loss or blindness was estimated, stratified when possible by factors including US state, age group, sex, race/ethnicity, and community-dwelling or group-quarters status. Data analysis occurred from March 2018 to March 2020. Main Outcomes or Measures The prevalence of visual acuity loss (defined as a best-corrected visual acuity greater than or equal to 0.3 logMAR) and blindness (defined as a logMAR of 1.0 or greater) in the better-seeing eye. Results For 2017, this meta-analysis generated an estimated US prevalence of 7.08 (95% uncertainty interval, 6.32-7.89) million people living with visual acuity loss, of whom 1.08 (95% uncertainty interval, 0.82-1.30) million people were living with blindness. Of this, 1.62 (95% uncertainty interval, 1.32-1.92) million persons with visual acuity loss are younger than 40 years, and 141 000 (95% uncertainty interval, 95 000-187 000) persons with blindness are younger than 40 years. Conclusions and Relevance This analysis of all available data with modern methods produced estimates substantially higher than those previously published.
TL;DR: In this paper, a double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized.
Abstract: Importance Open-angle glaucoma may continue to progress despite significant lowering of intraocular pressure (IOP). Preclinical research has suggested that enhancing mitochondrial function and energy production may enhance retinal ganglion cell survival in animal models of glaucoma, but there is scant information on its effectiveness in a clinical setting. Objective To test the hypothesis that a combination of nicotinamide and pyruvate can improve retinal ganglion cell function in human glaucoma as measured with standard automated perimetry. Design, setting, and participants In this phase 2, randomized, double-blind, placebo-controlled clinical trial at a single academic institution, 197 patients were assessed for eligibility. Of these, 42 patients with treated open-angle glaucoma and moderate visual field loss in at least 1 eye were selected for inclusion and randomized. A total of 32 completed the study and were included in the final analysis. The mean (SD) age was 64.6 (9.8) years. Twenty-one participants (66%) were female. Participant race and ethnicity data were collected via self-report to ensure the distribution reflected that observed in clinical practice in the US but are not reported here to protect patient privacy. Recruitment took place in April 2019 and patients were monitored through December 2020. Data were analyzed from January to May 2021. Interventions Ascending oral doses of nicotinamide (1000 to 3000 mg) and pyruvate (1500 to 3000 mg) vs placebo (2:1 randomization). Main outcomes and measures Number of visual field test locations improving beyond normal variability in the study eye. Secondary end points were the rates of change of visual field global indices (mean deviation [MD], pattern standard deviation [PSD], and visual field index [VFI]). Results Twenty-two of 29 participants (76%) randomized to the intervention group and 12 of 13 participants (92%) randomized to placebo received their allocation, and 32 participants (32 eyes; ratio 21:11) completed the study (21 from the intervention group and 11 from the placebo group). Median (IQR) follow-up time was 2.2 (2.0-2.4) months. No serious adverse events were reported during the study. The number of improving test locations was significantly higher in the treatment group than in the placebo group (median [IQR], 15 [6-25] vs 7 [6-11]; P = .005). Rates of change of PSD suggested improvement with treatment compared with placebo (median, -0.06 vs 0.02 dB per week; 95% CI, 0.02 to 0.24; P = .02) but not MD (0.04 vs -0.002 dB per week; 95% CI, -0.27 to 0.09; P = .35) or VFI (0.09 vs -0.02% per week; 95% CI, -0.53 to 0.36; P = .71). Conclusions and relevance A combination of nicotinamide and pyruvate yielded significant short-term improvement in visual function, supporting prior experimental research suggesting a role for these agents in neuroprotection for individuals with glaucoma and confirming the need for long-term studies to establish their usefulness in slowing progression. Trial registration ClinicalTrials.gov Identifier: NCT03797469.
TL;DR: An increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate, and may be associated with a simultaneous myopic shift in the Dutch population.
Abstract: Importance The incidence of rhegmatogenous retinal detachment (RRD) is partly determined by its risk factors, such as age, sex, cataract surgery, and myopia. Changes in the prevalence of these risk factors could change RRD incidence in the population. Objective To determine whether the incidence of RRD in the Netherlands has changed over recent years and whether this change is associated with an altered prevalence of RRD risk factors. Design, Setting, and Participants This cohort study included data from all 14 vitreoretinal clinics in the Netherlands, as well as a large Dutch population-based cohort study. All patients who underwent surgical repair for a primary RRD in the Netherlands from January 1 to December 31, 2009, and January 1 to December 31, 2016, were analyzed, in addition to all participants in the population-based Rotterdam Study who were examined during these years. Analysis began February 2018 and ended November 2019. Exposures RRD risk factors, including age, male sex, cataract extraction, and myopia. Main Outcomes and Measures Age-specific RRD incidence rate in the Dutch population, as well as change in RRD incidence and risk factor prevalence between 2009 and 2016. Results In 2016, 4447 persons (median [range] age, 61 [3-96] years) underwent surgery for a primary RRD within the Netherlands, resulting in an RRD incidence rate of 26.2 per 100 000 person-years (95% CI, 25.4-27.0). The overall RRD incidence rate had increased by 44% compared with similar data from 2009. The increase was observed in both phakic (1994 in 2009 to 2778 in 2016 [increase, 39%]) and pseudophakic eyes (1004 in 2009 to 1666 in 2016 [increase, 66%]), suggesting that cataract extraction could not solely account for the overall rise. Over the same period, the prevalence of mild, moderate, and severe myopia among persons aged 55 to 75 years had increased by 15.6% (881 of 4561 [19.3%] vs 826 of 3698 [22.3%]), 20.3% (440 of 4561 [9.6%] vs 429 of 3698 [11.6%]), and 26.9% (104 of 4561 [2.3%] vs 107 of 3698 [2.9%]), respectively, within the population-based Rotterdam Study. Conclusions and Relevance In this study, an increase was observed in primary RRD incidence in the Netherlands over a 7-year period, which could not be explained by a different age distribution or cataract surgical rate. A simultaneous myopic shift in the Dutch population may be associated, warranting further population-based studies on RRD incidence and myopia prevalence. This cohort study assesses whether the incidence of rhegmatogenous retinal detachment has changed over recent years and whether this change is associated with an altered prevalence of rhegmatogenous retinal detachment risk factors in the Netherlands. Question What is the incidence of primary rhegmatogenous retinal detachment (RRD) in the Netherlands and has it changed over recent years? Findings In this cohort study, 4447 individuals in the Netherlands underwent surgery for RRD in 2016, resulting in an incidence of 26.2 per 100 000 inhabitants, an increase of 44% compared with similar data from 2009. Over the same period, an increase in myopia prevalence in a Dutch population-based cohort study was observed. Meaning In the Netherlands, an increase in RRD incidence may be associated with a simultaneous myopic shift in the population.
TL;DR: Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation.
Abstract: Importance Glaucoma-related adverse events constitute serious complications of cataract removal in infancy, yet long-term data on incidence and visual outcome remain lacking. Objective To identify and characterize incident cases of glaucoma and glaucoma-related adverse events (glaucoma + glaucoma suspect) among children in the Infant Aphakia Treatment Study (IATS) by the age of 10.5 years and to determine whether these diagnoses are associated with optic nerve head (ONH) and peripapillary retinal nerve fiber layer (RNFL) assessment. Design, Setting, and Participants Analysis of a multicenter randomized clinical trial of 114 infants with unilateral congenital cataract who were aged 1 to 6 months at surgery. Data on long-term glaucoma-related status and outcomes were collected when children were 10.5 years old (July 14, 2015, to July 12, 2019) and analyzed from March 30, 2019, to August 6, 2019. Interventions Participants were randomized at cataract surgery to either primary intraocular lens (IOL), or aphakia (contact lens [CL]). Standardized definitions of glaucoma and glaucoma suspect were created for IATS and applied for surveillance and diagnosis. Main Outcomes and Measures Development of glaucoma and glaucoma + glaucoma suspect in operated-on eyes up to age 10.5 years, plus intraocular pressure, axial length, RNFL (by optical coherence tomography), and ONH photographs. Results In Kaplan-Meier analysis, for all study eyes combined (n = 114), risk of glaucoma after cataract removal rose from 9% (95% CI, 5%-16%) at 1 year, to 17% (95% CI, 11%-25%) at 5 years, to 22% (95% CI, 16%-31%) at 10 years. The risk of glaucoma plus glaucoma suspect diagnosis after cataract removal rose from 12% (95% CI, 7%-20%) at 1 year, to 31% (95% CI, 24%-41%) at 5 years, to 40% (95% CI, 32%-50%) at 10 years. Risk of glaucoma and glaucoma plus glaucoma suspect diagnosis at 10 years was not significantly different between treatment groups. Eyes with glaucoma (compared with eyes with glaucoma suspect or neither) had longer axial length but relatively preserved RNFL and similar ONH appearance and visual acuity at age 10 years. Conclusions and Relevance Risk of glaucoma-related adverse events continues to increase with longer follow-up of children following unilateral cataract removal in infancy and is not associated with primary IOL implantation. Development of glaucoma (or glaucoma suspect) after removal of unilateral congenital cataract was not associated with worse visual acuity outcomes at 10 years. Trial Registration ClinicalTrials.gov Identifier:NCT00212134
TL;DR: In this paper, the authors evaluated perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care, and found that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up.
Abstract: Importance Patient perceptions regarding the risks of obtaining in-person ophthalmic care during the coronavirus disease 2019 (COVID-19) pandemic may affect adherence to recommended treatment plans and influence visual outcomes. A deeper understanding of patient perspectives will inform strategies to optimize adherence with vision-preserving therapies. Objective To evaluate perceptions of COVID-19 exposure risk and their association with appointment attendance among patients at high risk of both reversible and irreversible vision loss from lapses in care. Design, Setting, and Participants This survey study included a nonvalidated telephone survey designed in April and May of 2020 and a retrospective medical record review conducted in parallel with survey administration from May 22 to August 18, 2020. Participants were recruited from 2 tertiary eye care centers (Emory Eye Center in Atlanta, Georgia, and W.K. Kellogg Eye Center in Ann Arbor, Michigan). The study included a random sample of patients with diagnoses of exudative age-related macular degeneration (AMD) or diabetic retinopathy (DR) who received an intravitreal injection between January 6 and March 13, 2020, and were scheduled for a second injection between March 13 and May 6, 2020. Main Outcomes and Measures Association between perceptions regarding COVID-19 risks and loss to follow-up. Results Of 1004 eligible patients, 423 (42%) were successfully contacted, and 348 (82%) agreed to participate (participants’ mean [SD] age, 75 [12] years; 195 women [56%]; 287 White [82%] patients). Respondents had a mean (SD) of 2.7 (1.1) comorbidities associated with severe COVID-19, and 77 (22%) knew someone with COVID-19. Of all respondents, 163 (47%) were very concerned or moderately concerned about vision loss from missed treatments during the pandemic. Although 208 (60%) believed the COVID-19 virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exposure at the eye clinic was extremely unlikely or unlikely, 49 (14%) believed it was extremely likely or likely. Seventy-eight participants (22%) were lost to follow-up. Concern regarding COVID-19 exposure during clinic visits (odds ratio [OR], 3.9; 95% CI, 1.8-8.4) and diagnosis of DR (vs AMD) (OR, 8.130; 95% CI, 3.367-20.408) were associated with an increase in likelihood of loss to follow-up. Conclusions and Relevance Among patients at high risk for vision loss from lapses in care, many expressed concerns regarding the effect of the pandemic on their ability to receive timely care. Survey results suggest that fear of SARS-CoV-2 exposure was associated with a roughly 4-fold increase in the odds of patient loss to follow-up. These results support the potential importance of clearly conveying infection-control measures.
Johns Hopkins University School of Medicine1, NewYork–Presbyterian Hospital2, New York University3, University of Miami4, University of Wisconsin-Madison5, Cleveland Clinic6, Massachusetts Eye and Ear Infirmary7, Thomas Jefferson University8, Duke University9, Rutgers University10, University of Illinois at Chicago11, Stanford University12, University of Washington13, Vanderbilt University Medical Center14
TL;DR: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase.
Abstract: Importance: The American Academy of Ophthalmology (AAO) indicated that urgent or emergent vitreoretinal surgical procedures should continue during the coronavirus disease 2019 (COVID-19) pandemic. Although decreases in the frequency of critical procedures have been reported outside the field of ophthalmology, analyses are limited by volume, geography, and time. Objective: To evaluate whether the frequency of ophthalmic surgical procedures deemed urgent or emergent by the AAO changed across the United States during the COVID-19 pandemic. Design, Setting, and Participants: Vitreoretinal practices from 17 institutions throughout the US participated in this multicenter cross-sectional study. The frequency of 11 billed vitreoretinal Current Procedural Terminology (CPT) codes across respective weeks was obtained from each practice between January 1, 2019, and May 31, 2020. Data were clustered into intravitreal injections (code 67028), lasers and cryotherapy (codes 67141, 67145, and 67228), retinal detachment (RD) repairs (codes 67107, 67108, 67110, and 67113), and other vitrectomies (codes 67036, 67039, and 67040). Institutions were categorized by region (Northeast, Midwest, South, and West Coast), practice setting (academic [tax-exempt] or private [non-tax-exempt]), and date of respective statewide stay-at-home orders. Main Outcomes and Measures: Nationwide changes in the frequency of billing for urgent or emergent vitreoretinal surgical procedures during the COVID-19 pandemic. Results: A total of 526â¯536 CPT codes were ascertained: 483â¯313 injections, 19â¯257 lasers or cryotherapy, 14â¯949 RD repairs, and 9017 other vitrectomies. Relative to 2019, a weekly institutional decrease in injections was observed from March 30 to May 2, 2020, with a maximal 38.6% decrease (from a mean [SD] of 437.8 [436.3] to 273.8 [269.0] injections) from April 6 to 12, 2020 (95% CI, -259 to -69 injections; P = .002). A weekly decrease was also identified that spanned a longer interval, at least until study conclusion (March 16 to May 31, 2020), for lasers and cryotherapy, with a maximal 79.6% decrease (from a mean [SD] of 6.6 [7.7] to 1.5 [2.0] procedures) from April 6 to 12, 2020 (95% CI, -6.8 to -3.3 procedures; P < .001), for RD repairs, with a maximal 59.4% decrease (from a mean [SD] of 3.5 [4.0] to 1.6 [2.2] repairs) from April 13 to 19, 2020 (95% CI, -2.7 to -1.4 repairs; P < .001), and for other vitrectomies, with a maximal 84.3% decrease (from a mean [SD] of 3.0 [3.1] to 0.4 [0.8] other vitrectomies) from April 6 to 12, 2020 (95% CI, -3.3 to -1.8 other vitrectomies; P < .001). No differences were identified by region, setting, or state-level stay-at-home order adjustment. Conclusions and Relevance: Although the AAO endorsed the continued performance of urgent or emergent vitreoretinal surgical procedures, the frequency of such procedures throughout the country experienced a substantial decrease that may persist after the COVID-19 pandemic's initial exponential growth phase. This decrease appears independent of region, setting, and state-level stay-at-home orders. It is unknown to what extent vitreoretinal intervention would have decreased without AAO recommendations, and how the decrease is associated with outcomes. Although safety is paramount during the COVID-19 pandemic, practices should consider prioritizing availability for managing high-acuity conditions until underlying reasons for the reduction are fully appreciated.
TL;DR: This study found that pathogenic variants amenable to base editing commonly occur in inherited retinal degeneration, and this findings, if generalized to other cohorts, provide an approach for developing base editing therapies to treat retina degeneration not isenable to gene therapy.
Abstract: Importance Many common inherited retinal diseases are not easily treated with gene therapy. Gene editing with base editors may allow the targeted repair of single-nucleotide transition variants in DNA and RNA. It is unknown how many patients have pathogenic variants that are correctable with a base editing strategy. Objective To assess the prevalence and spectrum of pathogenic single-nucleotide variants amenable to base editing in common large recessively inherited genes that are associated with inherited retinal degeneration. Design, Setting, and Participants In this retrospective cross-sectional study, nonidentifiable records of patients with biallelic pathogenic variants of genes associated with inherited retinal degeneration between July 2013 and December 2019 were analyzed using data from the Oxford University Hospitals Medical Genetics Laboratories, the Leiden Open Variation Database, and previously published studies. Six candidate genes (ABCA4, CDH23, CEP290, EYS, MYO7A,andUSH2A), which were determined to be the most common recessive genes with coding sequences not deliverable in a single adeno-associated viral vector, were examined. Data were analyzed from April 16 to May 11, 2020. Main Outcomes and Measures Proportion of alleles with a pathogenic transition variant that is potentially correctable with a base editing strategy and proportion of patients with a base-editable allele. Results A total of 12 369 alleles from the Leiden Open Variation Database and 179 patients who received diagnoses through the genetic service of the Oxford University Hospitals Medical Genetics Laboratories were analyzed. Editable variants accounted for 53% of all pathogenic variants in the candidate genes contained in the Leiden Open Variation Database. The proportion of pathogenic alleles that were editable varied by gene; 63.1% of alleles inABCA4, 62.7% of alleles inCDH23, 53.8% of alleles inMYO7A, 41.6% of alleles inCEP290, 37.3% of alleles inUSH2A, and 22.2% of alleles inEYSwere editable. The 5 most common editable pathogenic variants of each gene accounted for a mean (SD) of 19.1% (9.5%) of all pathogenic alleles within each gene. In the Oxford cohort, 136 of 179 patients (76.0%) had at least 1 editable allele. A total of 53 of 107 patients (49.5%) with biallelic pathogenic variants in the geneABCA4and 16 of 56 patients (28.6%) with biallelic pathogenic variants in the geneUSH2Ahad 1 of the 5 most common editable alleles. Conclusions and Relevance This study found that pathogenic variants amenable to base editing commonly occur in inherited retinal degeneration. These findings, if generalized to other cohorts, provide an approach for developing base editing therapies to treat retinal degeneration not amenable to gene therapy.
TL;DR: This cohort study uses data from the French National Health Data System to assess the decline in the use of intravitreal anti–vascular endothelial growth factors before, during, and after pandemic-associated lockdown periods.
Abstract: This study quantified changes in the use of IVT anti-VEGF since the pandemic began in France. The study involved beneficiaries of the National Health Insurance scheme (covering about 77% of the French population, or 51.5 million people) using the Systeme National des Donnees de Sante (French National Health Data System) of individual anonymized pharmacy claims data. The study found that 33,292 individuals used IVT anti-VEGF drugs in 2020 before lockdown (20,146 women [60.5%];mean [SD] age, 77.3 [11.1] years), 87,316 during lockdown (52,461 women [60.1%];mean [SD] age, 76.8 [11.0] years), and 63,020 during reopening (38,593 women [61.2%];mean [SD] age, 77.5 [11.0] years). Compared with expected numbers, observed numbers of individuals using IVT anti-VEGF markedly decreased by up to 47.1% (a decrease of 7432 patients) during the 5 first weeks of lockdown (weeks 12-16, 2020) and remained at a low level until the last week of lockdown (-24.9% [4424 fewer patients] during week 19). During the 8 weeks of lockdown, the shortfall represented a decrease of 46,381 injections. A gradual but incomplete recovery was observed in the first 4 weeks of reopening (difference of -21.9% [4247 fewer patients] in week 20 to -4.2% [723 fewer patients] and -3.5% [581 fewer patients] in weeks 22 and 23). Baseline sex and age characteristics of the patient cohort remained similar for each period. The decrease was particularly marked (-65.3%) for treatment initiations during lockdown. This decrease corresponds to a total of 8169 fewer treatment initiations during the lockdown period. A gradual recovery was observed during reopening.
TL;DR: In this article, the axial length in adults with high myopia was found to increase with the age, sex, best-corrected visual acuity (BCVA), and the presence or absence of choroidal neovascularization (CNV).
Abstract: Importance Pathologic myopia due to an excessive increase of axial length is associated with severe visual impairments. Systematic analyses to determine the rate of and the risk factors associated with the axial elongation in adults with high myopia based on long-term follow-up of a large population are needed. Objective To determine the risk factors associated with axial elongation in adults with high myopia. Design, setting, and participants This cohort study used the medical records of 43 201 patient visits in a single-hospital database that were collected from January 3, 2011, to December 28, 2018. A total of 15 745 medical records with the patients' sex, best-corrected visual acuity (BCVA), axial length, type of myopic maculopathy, and the presence or absence of choroidal neovascularization (CNV) were reviewed. Data were analyzed from April 3, 2019, to August 5, 2020. Main outcomes and measures Changes in the axial length at each examination were calculated. The significance of the associations between the annual increase of the axial length and age, sex, baseline axial length, types of myopic maculopathy, and a history of CNV was determined. Generalized linear mixed models were used to evaluate the strength of the risk factors associated with an increase of the axial length in high myopia. Results Among 1877 patients with 9161 visits included in the analysis, the mean (SD) age was 62.10 (12.92) years, and 1357 (72.30%) were women. The mean (SD) axial length was 29.66 (2.20) mm with a mean (SD) growth rate of 0.05 (0.24) mm/y. Among the 9161 visits, 7096 eyes (77.46%) had myopic maculopathy and 2477 eyes (27.04%) had CNV. The odds ratio for inducing a severe elongation of the axial length was 1.46 (95% CI, 1.38-1.55) for female sex, 0.44 (95% CI, 0.35-0.56) to 0.63 (95% CI, 13 0.50-0.78) for older than 40 years, 1.33 (95% CI, 1.15-1.54) for BCVA of less than 20/400, 1.67 (95% CI, 1.54-1.81) to 2.67 (95% CI, 2.46-2.88) for baseline axial length of 28.15 mm or greater, 1.06 (95% CI, 0.96-1.17) to 1.39 (95% CI, 1.24-1.55) for the presence of maculopathy, and 1.37 (95% CI, 1.29-1.47) for prior CNV. Conclusions and relevance This cohort study found continuing axial elongation in adults with high myopia. The risk factors for elongation do not appear to be modifiable, so prevention of myopia may be the best approach to reduce the incidence of pathologic myopia and its complications in the future.
TL;DR: In this paper, the authors investigated the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD.
Abstract: Importance Retinal biomarkers reflecting in vivo brain Alzheimer disease (AD) pathologic abnormalities could be a useful tool for screening cognitively normal (CN) individuals at the preclinical stage of AD. Objectives To investigate the association of both functional and structural alterations of the retina with in vivo AD pathologic abnormalities in CN older adults and model a screening tool for detection of preclinical AD. Design, Setting, and Participants This cross-sectional study included a total of 49 CN individuals, and all assessment was done at the Seoul National University Hospital, Seoul, South Korea. All participants underwent complete ophthalmic examination, including swept-source optical coherence tomography (SS-OCT) and multifocal electroretinogram as well as amyloid-β (Aβ) positron emission tomography and magnetic resonance imaging. Data were collected from January 1, 2016, through October 31, 2017, and analyzed from February 1, 2018, through June 30, 2020. Main Outcomes and Measures For structural parameters of the retina, the thickness of the macula and layer-specific thicknesses, including peripapillary retinal nerve fiber layer and ganglion cell-inner plexiform layer measured by SS-OCT, were used for analysis. For functional parameters of the retina, implicit time and amplitude of rings 1 to 6 measured by multifocal electroretinogram were used. Results Of the 49 participants, 25 were women (51.0%); mean (SD) age was 70.6 (9.4) years. Compared with 33 CN individuals without Aβ deposition (Aβ−CN), the 16 participants with Aβ (Aβ+CN) showed reduced inner nasal macular thickness (mean [SD], 308.9 [18.4] vs 286.1 [22.5] μm;P = .007) and retinal nerve fiber layer thickness, particularly in the inferior quadrant (133.8 [17.9] vs 103.8 [43.5] μm;P = .003). In addition, the Aβ+CN group showed prolonged implicit time compared with the Aβ−CN group, particularly in ring 5 (41.3 [4.0] vs 38.2 [1.3] milliseconds;P = .002). AD-related neurodegeneration was correlated with the thickness of the ganglion cell-inner plexiform layer only (r = 0.41,P = .005). The model to differentiate the Aβ+CN vs Aβ−CN groups derived from the results showed 90% accuracy. Conclusions and Relevance The findings of this study showing both functional as well as structural changes of retina measured by multifocal electroretinogram and SS-OCT in preclinical AD suggest the potential use of retinal biomarkers as a tool for early detection of in vivo AD pathologic abnormalities in CN older adults.
TL;DR: Patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years.
Abstract: Importance Although multiple imputation models for missing data and the use of mixed-effects models generally provide better outcome estimates than using only observed data or last observation carried forward in clinical trials, such approaches usually cannot be applied to visual outcomes from retrospective analyses of clinical practice settings, also called real-world outcomes. Objective To explore the potential usefulness of survival analysis techniques for retrospective clinical practice visual outcomes. Design, setting, and participants This retrospective cohort study covered a 12-year observation period at a tertiary eye center. Of 10 744 eyes with neovascular age-related macular degeneration receiving anti-vascular endothelial growth factor (VEGF) therapy between October 28, 2008, and February 1, 2020, 7802 eyes met study criteria (treatment-naive, first-treated eyes starting anti-VEGF therapy). Eyes were excluded from the analysis if they received photodynamic therapy or macular laser, any previous anti-VEGF therapy, treatment with anti-VEGF agents other than ranibizumab or aflibercept, or had an unknown date or visual acuity (VA) value at first injection. Main outcomes and measures Kaplan-Meier estimates and Cox proportional hazards modeling were used to consider VA reaching an Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 70 (Snellen equivalent, 20/40) or better, duration of VA sustained at or better than 70 (20/40), and VA declining to 35 (20/200) or worse. Results A total of 7802 patients (mean [SD] age, 78.7 [8.8] years; 4776 women [61.2%]; and 4785 White [61.3%]) were included in the study. The median time to attaining a VA letter score greater than or equal to 70 (20/40) was 2.0 years (95% CI, 1.87-2.32) after the first anti-VEGF injection. Predictive features were baseline VA (hazard ratio [HR], 1.43 per 5 ETDRS letter score or 1 line; 95% CI, 1.40-1.46), baseline age (HR, 0.88 per 5 years; 95% CI, 0.86-0.90), and injection number (HR, 1.12; 95% CI, 1.10-1.15). Of the 4439 of 7802 patients (57%) attaining this outcome, median time sustained at an ETDRS letter score of 70 (20/40) or better was 1.1 years (95% CI, 1.1-1.2). Conclusions and relevance In this cohort study, patients with neovascular age-related macular degeneration beginning anti-VEGF therapy were more likely to experience positive visual outcomes within the first 2.0 years after treatment, typically maintaining this outcome for 1.1 years but then deteriorating to poor vision within 8.7 years. These findings demonstrate the potential usefulness of the proposed analyses. This data set, combined with the statistical approach for retrospective analyses, may provide long-term prognostic information for patients newly diagnosed with this condition.
TL;DR: In this article, the authors describe the epidemiologic trend of pediatric eye exposures to alcohol-based hand sanitizers (ABHS) and report the severity of the ocular lesions, and support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population.
Abstract: Importance The coronavirus disease 2019 (COVID-19) pandemic has made alcohol-based hand sanitizers (ABHS) widely available in public places. This may warrant determining whether cases of unintentional ocular exposure are increasing, especially in children. Objective To describe the epidemiologic trend of pediatric eye exposures to ABHS and to report the severity of the ocular lesions. Design, Setting, and Participants Retrospective case series conducted from April 1, 2020, to August 24, 2020. Cases were retrieved from the national database of the French Poison Control Centers (PCC) and from a pediatric ophthalmology referral hospital in Paris, France. Cases of ocular exposure to chemical agents in children younger than 18 years during the study period were reviewed. Cases of ABHS exposure were included. Exposures The following data were collected: age, sex, circumstances of exposure, symptoms, size of the epithelial defect at first examination, time between the incident and re-epithelialization, and medical and/or surgical management. Main Outcomes and Measures Comparison of the number of eye exposures to ABHS in children between April to August 2020 and April to August 2019. Results Between April 1 and August 24, 2020, there were 7 times more pediatric cases of ABHS eye exposures reported in the PCC database compared with the same period in 2019 (9.9% of pediatric eye exposures in 2020 vs 1.3% in 2019; difference, 8.6%; 95% CI, 7.4-9.9;P Conclusions and Relevance These data support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population. To maintain good public compliance with hand disinfection, these findings support that health authorities should ensure the safe use of these devices and warn the parents and caregivers about their potential danger for children.
TL;DR: In this article, the authors compared photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months post-operatively.
Abstract: Importance Pneumatic retinopexy (PnR) is associated with superior visual acuity and reduced vertical metamorphopsia compared with pars plana vitrectomy (PPV) for primary rhegmatogenous retinal detachment (RRD). It is important to determine postoperative photoreceptor integrity with both surgical techniques. Objective To compare photoreceptor integrity on spectral domain-optical coherence tomography (SD-OCT) between PnR and PPV at 12 months postoperatively. Design, setting, and participants Post hoc analysis of the Pneumatic Retinopexy Versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) conducted between August 2012 and May 2017 at St Michael's Hospital, Toronto, Ontario, Canada. Primary RRDs with specific criteria were included. Data were analyzed between April and August 2020. Intervention Randomization to PnR vs PPV stratified by macular status. Main outcomes and measures Difference in proportion of patients with discontinuity of the ellipsoid zone (EZ) and external limiting membrane (ELM) between groups assessed independently by 2 masked graders at an external masked image reading center. Results A total of 150 participants completed the 12-month follow-up visit. A total of 145 patients (72 PPV and 73 PnR) had gradable spectral-domain optical coherence tomography at 12 months. Analysis of the central 3-mm (foveal) scans found that 24% (n = 17 of 72) vs 7% (n = 5 of 73) displayed EZ discontinuity (difference, 17%; odds ratio [OR], 4.204; 95% CI, 1.458-12.116; P = .005) and 20% (n = 14 of 71) vs 6% (n = 4 of 73) displayed ELM discontinuity (difference, 14%; OR, 4.237; 95% CI, 1.321-13.587; P = .01) in the PPV and PnR groups, respectively. Analysis of the 6-mm (foveal and nonfoveal) scans revealed that EZ and ELM discontinuity was greater in the PPV vs PnR groups (EZ, 32% [n = 23 of 72] vs 11% [n = 8 of 73]; difference, 21%; OR, 3.814; 95% CI, 1.573-9.249; P = .002; ELM, 32% [n = 23 of 71] vs 18% [n = 13 of 73]; difference, 14%; OR, 2.211; 95% CI, 1.015-4.819; P = .04). Conclusions and relevance Discontinuity of the EZ and ELM was more common at 12 months postoperatively following PPV vs PnR for RRD repair. The findings of this post hoc analysis suggest that less discontinuity of the EZ and ELM may provide an anatomic basis for the previously reported superior functional outcomes with PnR, although the analysis does not prove a cause-and-effect relationship. Trial registration ClinicalTrials.gov Identifier: NCT01639209.