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Venous thromboembolic complications have been reported in association with coronavirus disease 2019 (COVID-19) infection. We raised awareness regarding a potential temporal association between COVID-19 infection and retinal vein occlusion (RVO).Multicenter, retrospective, nonconsecutive case series.Patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection, were included. The exclusion criteria were as follows: age50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization.This was a multicenter, retrospective, nonconsecutive case series including patients presenting with hemi-RVO (HRVO) or central RVO (CRVO) between March 2020 and March 2021, with confirmed COVID-19 infection. The exclusion criteria were as follows: age50 years, hypertension, diabetes, glaucoma, obesity, underlying hypercoagulable states, and those requiring intubation during hospitalization.Ophthalmic findings, including presenting and final visual acuity (VA), imaging findings, and clinical course.Twelve eyes of 12 patients with CRVO (9 of 12) or HRVO (3 of 12) after COVID-19 infection were included. The median age was 32 years (range, 18-50 years). Three patients were hospitalized, but none were intubated. The median time from COVID-19 diagnosis to ophthalmic symptoms was 6.9 weeks. The presenting VA ranged from 20/20 to counting fingers, with over half (7 of 12) having a VA of ≥20/40. OCT revealed macular edema in 42% of the eyes; of these, 80% (4 of 5) were treated with anti-VEGF injections. Ninety-two percent (11 of 12) had partial or complete resolution of ocular findings at final follow-up. Four eyes (33%) had retinal thinning, as determined using OCT, by the end of the study interval. The final VA ranged from 20/20 to 20/60, with 11 of the 12 (92%) eyes achieving a VA of ≥20/40 at a median final follow-up period of 13 weeks (range, 4-52 weeks).Although we acknowledge the high seroprevalence of COVID-19 and that a causal relationship cannot be established, we reported this series to raise awareness regarding the potential risk of retinal vascular events due to a heightened thromboinflammatory state associated with COVID-19 infection.

Purpose Suboptimal functional outcomes following rhegmatogenous retinal detachment (RRD) repair may be related to photoreceptor abnormalities including alterations of the ellipsoid zone (EZ) which may not be apparent on cross-sectional optical coherence tomography (OCT). This study assessed EZ recovery using en face OCT following RRD repair and its association with visual acuity. Design Post hoc analysis of a randomized controlled trial. Methods Patients with macula-off RRD were followed at 3, 6, 12 and 24 months post-operatively and annually thereafter. En face OCT of the EZ slab were analyzed. Hyporeflective areas were co-localized with EZ abnormalities on cross-sectional OCT B-Scans and measured by two masked graders. Primary outcome was change in area of EZ hyporeflectivity from 3 to 24 months and its association with ETDRS visual acuity recovery was also assessed. Results 271 images of 61 patients were assessed. Mean area of hyporeflectivity significantly decreased from 3 to 24 months (-2.98 (95%CI,1.82-4.13) mm2, P Conclusions En face OCT provides a novel biomarker for visualizing and quantifying EZ recovery following RRD repair that is associated with ETDRS visual acuity recovery. A steady decline in the area of EZ hyporeflectivity was observed over many years with delayed recovery in patients with longer duration of macula-off.

Purpose To assess the incidence of post-operative outer retinal folds (ORFs) in pars plana vitrectomy (PPV) vs pneumatic retinopexy (PnR) following rhegmatogenous retinal detachment (RRD) repair and to determine the association of ORFs with functional outcomes at 1 year. Design Randomized controlled trial Participants Patients with primary macula-off RRD meeting PIVOT trial criteria randomly assigned to PPV vs PnR. Methods Post-hoc analysis of the PIVOT trial. Incidence and quantitative morphological features of ORFs were assessed with en face and cross-sectional OCT at 1 month post-operatively by two masked graders. ETDRS letter score and quantitative metamorphopsia were measured at 1 year. Main Outcome Measures Proportion of patients with ORFs following PPV vs PnR at 1 month post-operatively. Secondary outcomes include the association of ORFs with visual acuity (ETDRS letter score) and metamorphopsia (M-CHARTS) at 12 months post-operatively. Results Eighty-eight of the 176 participants enrolled in PIVOT were macula-off RRD. 94.3% (83/88) of these macula-off eyes had month 1 post-operative OCT scans that were gradable, 93.2% (41/44) in the PPV group and 95.5% (42/44) in the PnR group. The incidence of ORFs formation was 34.1% (14/41) in the PPV group and 14.3% (6/42) in the PnR group (p=0.034). ETDRS letter score at 1 year was 65.7±6.6 letters in patients with ORFs versus 75.1±1.4 letters in those without ORFs (difference=9.4 letters, 95% CI=7.5-11.3, p=0.047). Among patients in the PPV group only, mean ETDRS letter score at 1 year in patients with ORFs was 62.8 ± 24.7 letters compared to 75.4 ± 9.2 letters in patients without ORF formation (difference=12.6 letters, 95% CI=0.05-24.59, p=0.04). Horizontal and vertical metamorphopsia scores were similar in patients with vs without ORFs: horizontal: 0.35 ± 0.12 versus 0.29 ± 0.07 (difference=0.06, 95% CI=0.01-0.11, p=0.69) and vertical: 0.25±0.07 versus 0.29±0.07 (difference=0.04, 95%CI=0-0.08, p=0.60) respectively. There was a negative correlation between the closest distance of the ORFs from the fovea and the vertical metamorphopsia score (r=-0.507, p=0.045). Conclusions There is a greater risk of developing ORFs following PPV compared to PnR for RRD. ORFs at 1 month are associated with significantly worse ETDRS visual acuity letter score at 1 year.

KEY POINTS A healthy 20-year-old woman had a tuberculin skin test (TST), as required by her employer. Over 2 days, she developed a necrotizing reaction with a 1 cm central erosion surrounded by about 6 cm of induration with hyperpigmentation at the site of the TST ([Figure 1][1]). Six days later

The available literature regarding Oguchi disease is limited, with around 50 cases described to date. Caused by mutations to either the SAG gene coding for arrestin (Hayashi et al. in Ophthalmic Res 46:175–180, 2011) or the GRK1 gene coding for rhodopsin kinase (Yamamoto et al. in Nat Genet 15:175–178. https://doi.org/10.1038/ng0297-175 , 1997), Oguchi disease is an autosomal recessive condition with a good visual prognosis. The clinical diagnosis of the condition is based on the presence of night blindness (nyctalopia), as well as fundoscopic observation of the Mizuo–Nakamura phenomenon. The Mizuo–Nakamura phenomenon refers to a fundus discolouration described as a golden-brown colour with a yellow-grey metallic sheen most prominent in the peripheral retina; after prolonged dark adaptation, the fundus appears normal. The prevalence of Oguchi disease is highest in Japan, particularly with SAG mutations (Nakazawa et al. in Retina 17:17–22, 1997), although patients from Europe, Pakistan and India have also been described. Formal diagnosis requires genetic testing. Wide-field fundus images were obtained in both dark-adapted and light-adapted retina. Optical coherence tomography and dark-adapted electroretinography responses were used to further characterize the clinical phenotype. Existing descriptions of Oguchi disease have been limited by available technology. The flashes required for 45°-montage photographs in a dark-adapted eye quickly cause light adaptation. Recent advances in technology enable the capture of larger retinal areas in a single image. Wide-field 133° images were obtained of the native and dark-adapted fundus in natural colour. To our knowledge, these represent the first reported single-wide-field images of Oguchi disease, showing the characteristic Mizuo–Nakamura phenomenon in true colour. Genetic testing revealed a novel homozygous mutation in GRK1. Here, we demonstrate how characterizing this condition with single-shot true-colour wide-field imaging has distinct advantages over scanning laser technology, which applies artificial colouration, or stitched true-colour images. Images captured with wide-field systems create a much better representation of the native and dark-adapted fundus than can be observed by the ophthalmologist using direct fundoscopy and are essential in the clinical characterization of new mutations.

Pregnancy may be complicated by gestational diabetes mellitus (GDM) and/or microvascular complications like albuminuria, retinopathy and pre-eclampsia. In this study we aimed to identify whether mechanistic pathways associated with microvascular complications are active in pregnant women with GDM or microvascular disease.Urinary albumin excretion and biomarkers of inflammation, lipoprotein metabolism and tubular injury were quantified in 355 pregnant women with and without GDM. Participants underwent fundus photography graded for retinopathy. Adjusted associations between individual biomarkers and each outcome variable, including GDM status, albuminuria and retinopathy of interest, were performed using logistic regression.After adjusting for age, systolic blood pressure, body mass index and ethnicity, significant associations between GDM status and apolipoprotein A1, interleukin (IL)-6, IL-8, soluble tumour necrosis factor receptor-I and -II (sTNFR-I and -II), vascular endothelial growth factor and von Willebrand factor were observed. Increased high-sensitivity C-reactive protein (hsCRP) and sTNFR-II were associated with higher levels of albuminuria. hsCRP and previous GDM were associated with retinopathy.Mechanistic pathways associated with microvascular complications appear to be active in pregnant women with GDM or microvascular disease.

PurposeTo assess the incidence of persistent subfoveal fluid (PSFF) in pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) following rhegmatogenous retinal detachment (RRD) repair and to determine its association with functional outcomes.MethodsPosthoc analysis of the PIVOT randomised trial. Eyes with gradable en face and cross-sectional spectral-domain optical coherence tomography (SD-OCT) scans at 1–2 months postoperatively were included. Primary outcome was the proportion of patients with PSFF following PnR versus PPV at 1–2 months postoperatively. Secondary outcomes included association of PSFF with Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at 3, 6 and 12 months and metamorphopsia score (MCHARTs) at 12 months.ResultsOf 176 participants enrolled in PIVOT, 158 (89.8%) had gradable SD-OCT scans. Intergrader agreement was 0.870 (Cohen’s kappa). The incidence of PSFF was 16% (13/81) following PnR and 10.4% (8/77) following PPV (p=0.298; OR=1.65, 95% CI 0.64 to 4.23). Median ETDRS score at 3 months postoperatively between eyes with and without PSFF was 71 (IQR=58–78) and 78 (IQR=70–84), respectively (difference=7 letters, p=0.037), with no significant difference at subsequent 6-month and 12-month visits. Median metamorphopsia scores in patients with versus without PSFF were: horizontal: 0.1 (IQR=0–0.3) vs 0 (IQR=0–0.2) (difference=0.1, p=0.228) and vertical: 0.25 (IQR=0–0.4) vs 0 (IQR=0–0.2) (difference=0.25, p=0.148), respectively.ConclusionsThere was no significant difference in the incidence of PSFF in eyes undergoing PnR versus PPV for RRD. The presence of PSFF at 1–2 months postoperatively was associated with worse ETDRS letter score at 3 months, but there was no difference at 1 year.Trial registration numberNCT01639209.

To determine the association of aqueous humor cytokine concentrations with long-term treatment response to anti-vascular endothelial growth factor (VEGF) agents in diabetic macular edema (DME).Retrospective case series.Pooled data of aqueous humor cytokine concentrations collected at baseline and 2-month follow-up (2 injections) for treatment-naïve eyes with center-involving DME previously enrolled in a prospective study were reviewed. Subjects receiving intravitreal anti-VEGF injections outside of study protocol as per standard of care were classified into Responders versus Nonresponders based on qualitative assessment of optical coherence tomography for persistence of DME at longitudinal follow-up visits.Of the 41 eyes, 85% were classified as Responders with a significant decline in baseline central subfield thickness and macular volume (P values.001), and 15% were identified as Nonresponders to anti-VEGF therapy over 51.4 ± 18.7 months of follow-up. No significant difference in baseline aqueous humor VEGF concentration was noted, while at the 2-month follow-up the Nonresponder group had a significantly higher VEGF concentration compared with the Responder group (451.5 ± 690.9 pg/mL vs 113.7 ± 211.4 pg/mL; P = .02). The Responder group also demonstrated a significant decline from baseline to 2-month follow-up in concentration of intercellular adhesion molecule-1 (P.001), interleukin-10 (P = .041), monocyte chemotactic protein-1 (P = .046), placental growth factor (P = .027), and transforming growth factor-β2 (P = .017).Aqueous humor cytokine concentrations serve as an early biomarker for long-term response to anti-VEGF therapy and may enable more effective treatment regimens that improve anatomical outcomes in eyes with DME.

To assess the incidence of postoperative outer retinal folds (ORFs) after pars plana vitrectomy (PPV) vs. pneumatic retinopexy (PnR) for rhegmatogenous retinal detachment (RRD) repair and to determine the association of ORFs with functional outcomes at 1 year.Randomized controlled trial.Patients with primary macula-off RRD meeting the Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized (PIVOT) trial criteria who were randomly assigned to undergo PPV or PnR.Post hoc analysis of the PIVOT trial. The incidence and quantitative morphologic features of ORFs were assessed using en face and cross-sectional OCT at 1 month postoperatively by 2 masked graders. The ETDRS letter score was measured and quantitative assessment of metamorphopsia was performed at 1 year.Proportion of patients with ORFs at 1 month postoperatively among those who underwent PPV versus PnR. The secondary outcomes included the association of ORFs with visual acuity (ETDRS letter score) and metamorphopsia via metamorphopsia charts at 12 months postoperatively.Of 176 participants enrolled in PIVOT, 88 were macula-off RRDs. Of them, 94.3% (83 of 88) underwent postoperative OCT scans that were gradable at month 1, 93.2% (41 of 44) in the PPV group and 95.5% (42 of 44) in the PnR group. The incidence of ORF formation was 34.1% (14 of 41) in the PPV group and 14.3% (6 of 42) in the PnR group (P = 0.034). The ETDRS letter score at 1 year was 65.7 ± 6.6 letters in patients with ORFs vs. 75.1 ± 1.4 letters in those without ORFs (difference = 9.4 letters, 95% confidence interval [CI] = 7.5-11.3, P = 0.047). Among patients in the PPV group alone, the mean ETDRS letter score at 1 year in patients with ORFs was 62.8 ± 24.7 letters, compared with 75.4 ± 9.2 letters in patients without ORF formation (difference = 12.6 letters, 95% CI = 0.05-24.59, P = 0.04). Horizontal and vertical metamorphopsia scores were similar in patients with and without ORFs: horizontal, 0.35 ± 0.12 vs. 0.29 ± 0.07 (difference = 0.06, 95% CI = 0.01-0.11, P = 0.69); vertical, 0.25 ± 0.07 vs. 0.29 ± 0.07 (difference = 0.04, 95% CI = 0-0.08, P = 0.60). There was a negative correlation between the closest distance of an ORF from the fovea and vertical metamorphopsia score (r = -0.507, P = 0.045).There is greater risk of developing ORFs after PPV compared to PnR for primary RRD. Outer retinal folds at 1 month are associated with significantly worse ETDRS visual acuity letter scores at 1 year.

Consensus guidelines for the management of sarcoidosis recommend screening eye examinations for all patients, even in those without ocular symptoms. We aimed to determine the proportion of sarcoidosis patients that complete ophthalmologic evaluations and factors associated with their performance.We identified patients with sarcoidosis using population health services data from Ontario, Canada between 1991 and 2019. Sarcoidosis was defined by ≥ 2 physician visits for sarcoidosis within a two-year period. Ophthalmologic evaluations were based on an optometrist or ophthalmologist visit within the year prior or two years following the diagnosis. We estimated correlations between the number of eye care professionals and proportion of sarcoidosis patients completing ophthalmologic assessments within regional health units. We evaluated for associations between ophthalmologic screening and patient characteristics using multivariable logistic regression.We identified 21,679 patients with sarcoidosis in Ontario. An ophthalmologic evaluation was performed in 14,751 (68.0%), with a similar number of individuals seeing ophthalmologists and optometrists (43.7% vs. 42.2%). The percentage of sarcoidosis patients undergoing an ophthalmologic evaluation within corresponding regional health units was moderately correlated with the number of practicing ophthalmologists (r = 0.64, p = 0.01), but not the number of optometrists (r = 0.08, p = 0.77). Patients who were older [OR per year 1.02 (95% CI 1.01-1.02), p 0.001] and female [OR 1.54 (95% CI 1.44-1.63), p 0.001] were more likely to complete ophthalmologic evaluations. Immigrants to Canada were less likely to undergo ophthalmologic assessments [OR 0.66 (95% CI 0.60-0.73), p 0.001].Most patients with sarcoidosis complete ophthalmologic examinations, though a substantial proportion does not. Young adults, men and immigrants were less likely to complete ophthalmologic evaluations. Limited access to ophthalmologists may at least in part explain why some sarcoidosis patients fail to complete ophthalmologic screening.

Importance Although rhegmatogenous retinal detachment (RRD) repair techniques have high anatomical reattachment rates, there may be differences in various aspects of postoperative vision-related quality of life (VRQoL). Objective To explore the differences in various aspects of VRQoL between pneumatic retinopexy (PnR) and pars plana vitrectomy (PPV) following RRD repair. Design, Setting, and Participants Post hoc exploratory analysis of the the Pneumatic Retinopexy vs Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes randomized clinical trial conducted between August 2012 and May 2017 at St Michael’s Hospital, Toronto, Ontario, Canada. Patients with RRD with a single break or multiple breaks within 1 clock hour of detached retina in the superior 8 clock hours of the retina with any number, location, and size of retinal breaks or lattice degeneration in attached retina. Main Outcomes and Measures Differences in the 25-Item National Eye Institute Visual Function Questionnaire 12 subscale scores between the PnR and PPV groups at 6 months following RRD repair. Results A total of 160 patients were included in this analysis, with 81 patients (92%) and 79 patients (90%) in the PnR and PPV groups, respectively. The PnR group consisted of 32% women with a mean (SD) age of 60.9 (9.3) years, while the PPV group consisted of 38% women with a mean (SD) age of 60.3 (7.6) years. For the 152 patients with 6-month follow-up (75 patients in PnR [85%] and 77 patients in PPV [88%]), there was evidence for an association of PnR with superior vision-related functioning compared with PPV for several subscales. There were no differences between groups at 1 year. After adjusting for age, sex, baseline macular status, visual acuity in the nonstudy eye, and lens status, patients who underwent PnR had higher scores for distance activities (mean [SD] PnR, 88.7 [13.4]; PPV, 82.8 [17.1]; adjusted difference, 6.5; 95% CI, 1.6-11.4;P = .01), mental health (mean [SD] PnR, 84.3 [17.4]; PPV, 78.7 [21.1]; adjusted difference, 6.7; 95% CI, 0.4-13;P = .04), dependency (mean [SD] PnR, 96.1 [10.1]; PPV, 91.1 [18.6]; adjusted difference, 5.7; 95% CI, 0.6-10.8;P = .03), and peripheral vision (mean [SD] PnR, 91.6 [16.2]; PPV, 81.2 [24.4]; adjusted difference, 10.8; 95% CI, 4.3-17.4;P = .001) at 6 months. Conclusions and Relevance These findings demonstrate that patients undergoing PnR for RRD report higher mental health scores and superior vision-related functioning scores in several subscales of the 25-Item National Eye Institute Visual Function Questionnaire during the first 6 months postoperatively compared with PPV. Trial Registration ClinicalTrials.gov Identifier:NCT01639209.

Central retinal artery occlusion (CRAO) is a devastating disease resulting in severe visual loss in most cases. It has no proven treatment, and a variety of management options used clinically all have dismal rate of success. We report outcome of treatment with local intra-arterial thrombolysis administered 2.75 hours after devastating visual loss from incomplete CRAO.

To assess the characteristics of referrals to academic uveitis tertiary care centres in Toronto and identify determinants of wait time for consultation.Retrospective case series.Consecutive new uveitis referrals received at 5 University of Toronto-affiliated uveitis tertiary care centres, between February 2016 and November 2016, were included.A total of 159 new uveitis referrals were received from academic (69%) and community (31%) providers. A large proportion of referrals were sent by comprehensive ophthalmologists (33%) and retina specialists (38%). Disease was bilateral in 46% of cases, had an acute onset in 43% of cases, and was classified as posterior uveitis in 38% of cases. Disease etiology at the time of referral was unknown in 55% of cases. Only 43% of all referrals included a basic uveitis workup, and patients who had undergone diagnostic testing had a shorter wait time for consultation (41 ± 43 vs. 59 ± 54 days, p = 0.033). Acute uveitis had a shorter wait time compared with recurrent and chronic uveitis (33 ± 42 vs. 66 ± 44 and 59 ± 58 days, p0.001). Referrals triaged as urgent had significantly shorter wait times compared with referrals triaged as semiurgent or elective (7 ± 10 vs. 54 ± 43 and 88 ± 59, p0.001).Referrals to academic uveitis tertiary care centres in Toronto are often acute, bilateral cases affecting the posterior segment without a known etiology. Approximately half of referrals include no diagnostic workup, which may delay diagnosis for patients and lengthen wait times for consultation. We provide a set of recommendations for investigations that should be included in uveitis referrals.

Objective To assess how polypoidal choroidal vasculopathy (PCV) is recognized and treated, and to assess whether treatment outcomes are different between Chinese and Caucasian Canadian patients with age-related macular degeneration (AMD). Design Retrospective chart review. Participants 154 eyes from 135 Chinese patients and 2291 eyes from 1792 Caucasian patients who were newly diagnosed with either AMD or PCV and had more than 1 year of follow-up were included. Methods All newly diagnosed AMD patients presenting to the Retina Service of 3 Toronto University Hospitals, between March 25, 2008, to September 30, 2014, were reviewed. Results 10/154 eyes (6.5%) in Chinese Canadians and 16/2291 eyes (0.7%) in Caucasian Canadians were diagnosed as having PCV. Indocyanine green angiography (ICGA) was used to diagnose PCV in 20% of Chinese Canadians and 8.8% of Caucasian Canadians. Clinical practices with a larger percentage of Chinese patients were more likely to diagnose PCV in both Chinese ( p = 0.004) and Caucasian patients ( p = 0.03), were more likely to use photodynamic therapy (PDT) ( p p Conclusion Our study has shown that PCV is under-recognized in a Canadian population, and ICGA is underutilized. In clinical practices with a greater portion of Chinese patients, PCV is more often recognized and PDT is used more liberally.

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.

Purpose The optimal surgery to repair rhegmatogenous retinal detachment (RRD) is unknown. The purpose of this trial was to compare outcomes of pneumatic retinopexy (PnR) versus pars plana vitrectomy (PPV) for the management of primary RRD. Design Prospective, randomized controlled trial. Participants Patients with RRD demonstrating a single retinal break or a group of breaks in detached retina within 1 clock hour above the 8- and 4-o’clock meridians, with any number, location and size of retinal breaks or lattice degeneration in attached retina. Methods Patients were randomized to undergo either PnR or PPV. Macula-on and macula-off patients were assigned to intervention group by stratified randomization and were treated within 24 and 72 hours, respectively. Main Outcome Measures The primary outcome was 1-year Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA). Important secondary outcomes were subjective visual function (25-item National Eye Institute Visual Function Questionnaire), metamorphopsia score (M-CHARTS), and primary anatomic success. Results One hundred seventy-six patients were recruited between August 2012 and May 2016. ETDRS VA after PnR exceeded that after PPV by 4.9 letters at 12 months (79.9±10.4 letters vs. 75.0±15.2 letters; P = 0.024). Mean ETDRS VA also was superior for the PnR group compared with the PPV group at 3 months (78.4±12.3 letters vs. 68.5±17.8 letters) and 6 months (79.2±11.1 letters vs. 68.6±17.2 letters). Composite 25-item National Eye Institute Visual Function Questionnaire scores were superior for PnR at 3 and 6 months. Vertical metamorphopsia scores were superior for the PnR group compared with the PPV group at 12 months (0.14±0.29 vs. 0.28±0.42; P = 0.026). Primary anatomic success at 12 months was achieved by 80.8% of patients undergoing PnR versus 93.2% undergoing PPV (P = 0.045), with 98.7% and 98.6%, respectively, achieving secondary anatomic success. Sixty-five percent of phakic patients in the PPV arm underwent cataract surgery in the study eye before 12 months versus 16% in the PnR group (P Conclusions Pneumatic retinopexy should be considered the first line treatment for RRD in patients fulfilling Pneumatic Retinopexy versus Vitrectomy for the Management of Primary Rhegmatogenous Retinal Detachment Outcomes Randomized Trial (PIVOT) recruitment criteria. Pneumatic retinopexy offers superior VA, less vertical metamorphopsia, and reduced morbidity when compared with PPV.

When encountering patients with markedly dilated and tortuous retinal vessels, Wyburn-Mason syndrome (WMS) or racemous angiomatosis (phacomatosis) is commonly thought of as the archetypal entity that can produce these findings. We describe a patient with Cantu syndrome with phenotypical findings identical to those seen in patients with WMS and want to highlight this as another entity that can present with tortuous and dilated retinal vessels.

To determine whether aqueous cytokine levels correlate with disease severity in diabetic macular edema.A prospective cross-sectional study of 49 adults with diabetes mellitus, centre-involving diabetic macular edema and central subfield macular thickness ≥310 μm on spectral domain optical coherence tomography. Clinical examination and aqueous sampling were carried out before an initial injection of ranibizumab. Multiplex immunoassay of sample was carried out for vascular endothelial growth factor, placental growth factor, transforming growth factor beta, intercellular adhesion molecule-1, interleukin (IL)-2, IL-3, IL-6, IL-8, IL-10, IL-17, vascular cell adhesion molecule-1, monocyte chemoattractant protein-1, and epidermal growth factor. Multivariate robust regression models were constructed, and adjusted for age, lens status, or severity of retinopathy, and size of foveal avascular zone.Spectral domain optical coherence tomography macular volume was an excellent measure of disease severity, correlating strongly with central subfield macular thickness (P0.001), best-corrected Snellen visual acuity (P0.001), and baseline diabetic retinopathy severity (P = 0.01). Elevated aqueous intercellular adhesion molecule-1 correlated with greater macular volume (P = 0.002). No aqueous cytokine, including VEGF, correlated with central subfield macular thickness. There was an association between IL-10 levels and best-corrected Snellen visual acuity (P = 0.03).Aqueous intercellular adhesion molecule-1 correlates with disease severity as measured by macular volume on spectral domain optical coherence tomography, and IL-10 is associated with BCVA. Intercellular adhesion molecule-1 may be a clinically useful biomarker for diabetic macular edema severity.

IMPORTANCE: Variability in response to anti–vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. OBJECTIVES: To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. DESIGN, SETTING, AND PARTICIPANTS: In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. INTERVENTIONS: Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. MAIN OUTCOMES AND MEASURES: Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. RESULTS: Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, −190.88; interquartile range [IQR], −634.20 to −26.54; P

Is vergence state a reliable cue to absolute distance? The answer to this seemingly simple question has been the subject of a long-standing and controversial debate in the vision literature. It is somewhat sobering, but perhaps also an indication of the complexity of the problem, that vision researchers have not been able to communicate effectively with one another in order to answer deŽ nitively this question. A recent attempt to answer this question was undertaken by Logvinenko et al. (2001). These authors traced the issue back to Bishop Berkeley (1709/1910), who hypothesized that vergence might serve as a cue to absolute distance. In particular, Logvinenko et al. attempted to resolve this issue through studying the relation between vergence eye movements and the wallpaper illusion, a relation on which several authors have commented including Helmholtz (1910/ 1962), and concluded that vergence is not a reliable cue to absolute distance. To mention just one other study, Richards and Miller (1969) traced formal experimental attempts to answer this question to Wundt (1862) and cite Hillebrand (1893), Irvine and Ludvigh (1936), Gogel (1961) and Ogle (1962) as other authors who have also

We report on evidence for selective long-distance interactions in Cyclopean binocular vision. When presented with a pair of Cyclopean test bars observers could discriminate trial-to-trial uncorrelated variations in the mean orientation, orientation difference, separation and mean location of the test bars while ignoring random variations in the orientation, width and location of a third bar placed between the two test bars. We propose that the human visual system contains Cyclopean long-distance comparators (i) that compare the outputs of two narrow receptive fields some distance apart while being insensitive to stimuli located between those receptive fields, and (ii) the outputs of which carry orthogonally labelled indicators of orientation difference, mean orientation, separation and mean location. In the evolutionary context, one role for the proposed mechanisms might be to encode information about the silhouettes of animals whose camouflage is broken by the binocular vision of predators.

We measured Weber fractions for discriminating the speed of cyclopean gratings and Weber fractions for discriminating the speed of luminance gratings. Of our 14 observers, five were unable to see the cyclopean grating sufficiently well to discriminate its speed. One observer experienced great difficulty in discriminating the speed of cyclopean gratings, even though her threshold for detecting cyclopean gratings was low, and even though she discriminated the speed of luminance gratings on the basis of the task–relevent variable. But several observers based their speed discriminations on trial-to-trial variations of the task–relevent variable while ignoring associated trial-to-trial variations in all task–irrelevant variables (specifically: displacement; temporal frequency; spatial frequency; and presentation duration). We conclude that the visual systems of these observers contain a specialized neural mechanism for the speed of cyclopean gratings that supports acute discriminations of speed (Weber fractions were as low as 0.05–0.07).

Importance This study demonstrates that increasing quintiles of baseline high-sensitivity C-reactive protein (hsCRP) level may be associated with higher risk of incident clinically significant macular edema, the leading cause of vision loss in working-aged individuals in North America. Objective To determine whether baseline levels of hsCRP and intercellular adhesion molecule 1 (ICAM-1) predict development and progression of diabetic retinopathy (DR), clinically significant macular edema (CSME), retinal hard exudates, and proliferative DR in the Diabetes Control and Complications Trial (DCCT) cohort. Design The DCCT was a large multicenter randomized controlled clinical trial. Setting Twenty-nine medical centers in the United States and Canada. Participants The DCCT population consisted of 1441 subjects with type 1 diabetes mellitus aged 13 to 39 years at study entry. Intervention We measured levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 in stored baseline blood samples. Main Outcome Measures We assessed the association of levels of hsCRP, ICAM-1, vascular cell adhesion molecule 1, and tumor necrosis factor α receptor 1 with incident DR end points ascertained from grading of standardized 7-field stereoscopic retinal color photographs taken at baseline and every 6 months during follow-up. Results After adjustment for randomized treatment assignment and other factors, we observed a statistically significant association between hsCRP and risk of CSME, with a relative risk (RR) for the top vs bottom quintile of 1.83 (95% CI, 0.94-3.55; P for trend = .01). Similarly, for the development of retinal hard exudates, the RR for the top vs bottom quintile of hsCRP level was 1.78 (95% CI, 0.98-3.25; P for trend = .004), whereas for ICAM-1 level, the RR comparing the top vs bottom quintiles was 1.50 (95% CI, 0.84-2.68; P for trend = .05). There were no statistically significant associations between baseline VCAM-1 or tumor necrosis factor α receptor 1 levels and risk of any of the DR end points. Conclusions and Relevance After adjusting for known risk factors, increasing quintiles of baseline hsCRP level may be associated with higher risk of incident CSME and macular hard exudate in the DCCT cohort. Circulating levels of ICAM-1 may also be associated with the development of retinal hard exudates.

Objective: To report the results of pediatric choroidal neovascular membranes (CNVMs) secondary to a variety of etiologies treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents. Design: Retrospective case series. Participants: Four pediatric patients at the Hosptial for Sick Children with CNVMs secondary to a variety of etiologies. Methods: Each patient received multiple treatments with one of the following anti-VEGF agents: pegaptanib sodium, bevacizumab, or ranibizumab. Progress was monitored by clinical exam, optical coherence tomography (OCT), and fluorescein angiography. Results: The mean age of our patients was 11.5 years (range, 8–15 years). Patients were followed for a mean of 10 months (range, 4–14 months). One patient was treated with pegaptanib sodium, 2 with bevacizumab, and 1 with ranibizumab. Following treatment, 1 patient showed an improvement and 3 showed stabilization of vision with reduction of fluid on clinical exam and OCT, and cessation of leakage on the fluorescein angiogram. Patients required 2–5 injections of the anti-VEGF agent. No ocular or systemic adverse events were observed in any of our treated patients. Conclusions: Anti-VEGF agents were effective in the treatment of pediatric CNVMs in this case series. However, we do not know how these results would have differed from other treatment modalities, including observation. We did not observe any adverse side effects; however, larger studies are required to document the safety of these medications in the pediatric population where normal angiogenesis is occurring.

Pregnancy-associated retinal diseases are conditions that may occur uniquely in pregnancy or, more commonly, general conditions that may worsen or alter during pregnancy as a result of hematologic, hormonal, metabolic, cardiovascular, and immunologic changes. Diabetic retinopathy (DR) is by far the most common retinal condition that is altered by pregnancy. However, there are currently no widely accepted, precise clinical guidelines regarding its management during pregnancy. At present it is not possible to predict who will regress and who will progress without treatment. Some of the variation in progression of DR in pregnancy may be a result of well-known risk factors such as hypertension or inadequate glycemic control prior to pregnancy. Other pregnancy-associated retinal diseases are relatively uncommon, and their treatments are poorly characterized. Pre-existing conditions include the white dot syndromes, such as punctuate inner choroidopathy and ocular histoplasmosis syndrome, as well as chorioretinal neovascularization from many other etiologies. Retinal and chorioretinal disorders that can arise during pregnancy include central serous chorioretinopathy and occlusive vasculopathy such as retinal artery occlusion (Purtschers-like retinopathy) and retinal vein occlusion. There remains a small group that appear to be unique to pregnancy, with pre-eclampsia- and eclampsia-associated retinopathy, disseminated intravascular coagulopathy, or amniotic fluid embolism being the best described. In angiogenic retinal diseases outside of pregnancy, the use of anti-vascular endothelial growth factor (anti-VEGF agents) has proven helpful. There are no safety data about the use of anti-VEGF agents during pregnancy, and conventionally the proposed interventions have been laser photocoagulation and systemic or intravitreal injections of steroids. Most of the literature on the treatment of pregnancy associated-chorioretinal neovascularization is anecdotal.

Humans can compare the orientations and locations of two motion-defined test bars several degrees apart so as to rapidly encode and place in memory their mean orientation, orientation difference, separation and mean location, while ignoring stimuli located between the two test bars. Performance is not impaired by randomly varying the location of the bars. We conclude that the two test bars are not compared by shifting gaze location or attention from one test bar to the other, nor by attending to two spatial locations. In addition, observers can discriminate the orientation difference and mean orientation of two test bars that, each of which is rendered visible by a different sub-modality (motion, disparity or luminance). Taking into account the findings reported here and previously reported findings on the early processing of luminance-defined form (Vis. Res. 40 (2000) 2291, Vis. Res. 42 (2002) 49) and cyclopean form (Proc. Roy. Soc. Lond. B 268 (2001) 213) we propose that the human visual system contains a fast long-distance comparator that compares the orientation and locations of two test bars while being insensitive to stimuli in the space between the test bars, and that this process is independent of whether the test bars are rendered visible by only one of three kinds of contrast (luminance, disparity, motion) or by combinations of the three. One role of this comparator mechanism may be to rapidly bind the spatial aspects of the retinal image across sub-modalities immediately after each saccade.

The psychophysical data reported here indicate that observers can attend simultaneously to a pair of test lines while ignoring stimuli between the two test lines, and can extract independently four relationships between the two test lines. We measured discrimination thresholds for the mean orientation of a pair of lines as well as for their orientation difference, separation and mean location. We propose: (a) that all four discriminations were mediated by comparator mechanisms that received inputs from two first-stage narrow receptive fields whose centres were located some distance apart and which were “blind” to stimuli falling between the two receptive fields; (b) that the human visual system contains mechanisms of this kind whose outputs are labelled with the orientation difference, the mean orientation, the mean location, and the separation of the two first-stage receptive fields; (c) that orientation difference, mean orientation, separation, and mean locations are signalled independently. We found that all four discrimination thresholds were independent of test-line contrast for contrasts more than 2–3 times above line-detection contrast threshold. This finding can be understood if each of the four labelled outputs feeds an opponent-process stage. The preceding proposals can account for several previously reported phenomena. More generally, an array of the proposed long-distance comparator mechanisms constitutes a system that may be capable of fully specifying the shape, size, location and implicit orientation of the boundaries of an object’s retinal image.

Importance Treatment with intravitreal (IVT) injections has increased during the last several years as evidence has accumulated demonstrating the efficacy of anti–vascular endothelial growth factor agents in the treatment of neovascular age-related macular degeneration (AMD) and various retinal vascular diseases. Although IVT injections are generally safe, infectious endophthalmitis is a rare but devastating complication, and the risk of morbidity and vision loss from endophthalmitis is high. Objective To examine the change in antibiotic resistance of ocular surface flora with repeated prophylactic use of antibiotics after IVT injection for AMD. Design and Setting Prospective, nonrandomized cohort study in 2 tertiary academic hospitals. Participants Patients 65 years and older with newly diagnosed AMD were recruited by 7 retinal specialists from July 1, 2010, through December 31, 2011. Intervention The study group received topical moxifloxacin hydrochloride for 3 days after each monthly IVT injection. Main Outcome Measure Resistance to moxifloxacin and ceftazidime in cultured isolates at baseline and monthly for 3 months by change in minimal inhibitory concentration (MIC) of culture isolates was studied. Results The study group consisted of 84 patients, and the control group had 94 patients. In the study group, the baseline adjusted MIC increased (from 1.04 to 1.25 μg/mL; P = .01) as did the MIC for 50% of isolates (MIC50) (from 0.64 to 1.00 μg/mL) and the MIC for 90% of isolates (MIC90) (from 0.94 to 4.00 μg/mL). In both groups, the culture-positive rate did not change significantly when adjusted for baseline. No significant change was found in the MIC level, culture-positive rate, MIC50 level, and MIC90 level in the control group. Subgroup analysis found diabetes mellitus to be noncontributory to both the MIC and culture-positive rate. No endophthalmitis or adverse events were reported. Conclusions and Relevance Repeated use of topical moxifloxacin after IVT injection significantly increases antibiotic resistance of ocular surface flora. We recommend that routine use of prophylactic antibiotics after IVT injection be discouraged. Trial Registration clinicaltrials.gov Identifier: NCT01181713

Objectives The recent development of handheld spectral-domain optical coherence tomography (HHSD-OCT) has enabled us to obtain high-resolution retinal scans of premature infants with retinopathy of prematurity (ROP). The purpose of this study is to document HHSD-OCT findings in laser-treated neonates with progressive ROP. Methods This is a retrospective consecutive case series of 3 patients with progressive ROP despite laser photocoagulation. All patients were transferred from peripheral neonatal intensive care units (NICUs) to the Children's Hospital Los Angeles. All patients had a complete ocular examination, fundus photography, fluorescein angiography, and HHSD-OCT. Results All 3 patients had active progressive ROP despite prior laser photocoagulation. Of the 6 eyes, 1 was excluded from the study because it had an exudative retinal detachment following laser photocoagulation. Retinal detachment was not detected on clinical examination in the 5 remaining eyes, although there was vitreoretinal traction at the ridges of 3 of the 5 eyes. The HHSD-OCT identified presumed retinoschisis in all 5 study eyes. Conclusions Tractional retinoschisis may be an important finding in progressive laser-treated ROP, made possible by use of the HHSD-OCT. This finding may have significant implications for how we classify and treat patients whose ROP is progressing despite laser treatment. Furthermore, the use of the HHSD-OCT can provide valuable insight into the interaction of the retina, vitreous, and ridge in patients with progressive ROP, and it allows shallow detachments and retinoschisis to be diagnosed earlier and more accurately than would otherwise be possible.

Within a duration of 20 ms humans can compare the orientations of two test lines so as to encode and place in memory their mean orientation and orientation difference while ignoring noise lines in the space between the test lines. Furthermore, performance is not impaired by randomly varying the location of each test line from trial-to-trial. We conclude that the two test lines are not compared by shifting eye fixation or attention from one to the other, nor by attending to two spatial locations. This evidence is consistent with the proposal that the human visual system contains second-stage long-distance comparators, any one of which responds to simultaneous stimulation of two conventional first-stage spatial filters located some distance apart and is insensitive to stimuli that fall between these two first-stage filters. We suggest that our observers performed discriminations by attending to the outputs of the proposed second-stage long-distance comparators rather than by attending to two spatial locations. In addition to their mean orientation and orientation difference, humans can simultaneously encode and place in memory the separation and mean location of the two test lines while ignoring stimuli in the space between the lines. We suggest that, following each of the eye's exploratory saccades, the proposed second-stage long-distance comparators, in effect, take a snapshot of an object's retinal image that ignores the object's surface texture while encoding the shape of its boundary.

The psychophysical data reported here bear on how the boundaries of an object’s retinal image are processed in early vision. We propose that the visual system contains a mechanism sensitive to four relationships between two local stimuli some distance apart and that the output of this hypothetical mechanism encodes and labels orthogonally the four relationships. We measured the just-noticeable difference in the orientation difference between two test lines as well as the just-noticeable differences in their mean orientation, mean location, and separation. A pair of noise lines was located between the two test lines. By arranging that trial-to-trial variations in the orientation difference, mean orientation, mean location and separation of the test lines had zero correlation with each other and with trial-to-trial variations in the corresponding variables for the two noise lines we could demonstrate that psychophysical responses were based on the task-relevant variable and that, for each of the four task-relevant variables, all task-irrelevant variables were ignored. The finding that responses to the test lines were unaffected by the noise lines implies that discriminations were not influenced by first–stage spatial filters with strictly local receptive fields that responded to both test lines. Because these findings held for a presentation duration of 20 ms we can exclude the possibility that observers compared the two test lines by shifting either fixation or attention. We propose that, rather than by attending to two different locations, the test lines were selected by attending to the output of the long-distance comparator whose ‘separation’ label signaled the largest magnitude. The above proposals can account for several previously reported phenomena. More generally, an array of the proposed long-distance comparators constitutes a system that may be capable of specifying the shape, size, location and implicit orientation of an object’s retinal image.