Morphological and Functional Correlations in Acute Central Serous Chorioretinopathy.

PURPOSE: We evaluate morphological and functional correlations in patients with acute central serous chorioretinopathy (CSC). METHODS: A prospective study was conducted on 50 patients with an acute CSC episode lasting less than 3 months. At baseline, assessments included optical coherence tomography (OCT), best-corrected visual acuity (BCVA), contrast sensitivity (CS), microperimetry (MP), and multifocal electroretinography (mfERG). A correlation analysis between OCT morphological parameters (maximal subretinal fluid height (SRF), central retinal thickness (CRT), and macular volume (MV)) and functional parameters was conducted on the affected eye for each patient. RESULTS: Among the morphological parameters, SRF showed the strongest correlations with functional parameters (r absolute value range = 0.10-0.70). Weak correlations were observed between BCVA and morphological parameters (r absolute value range = 0.14-0.26). Average retinal sensitivity (MP-A) was the functional parameter displaying the most robust negative correlation with morphological parameters (r absolute value range = 0.61-0.70). In contrast, average contrast sensitivity (CS-A) and mfERG average amplitude density in the first (mfERG-A1) and second (mfERG-A2) ring showed weak to moderate (r absolute value range = 0.35-0.56) yet statistically significantly nonzero correlations. CONCLUSIONS: SRF and CRT could serve as the most representative morphological proxies for visual function deficit in acute CSC patients. Retinal sensitivity, as measured by MP, may be superior to BCVA in clinical research studies or when an in-depth visual function evaluation is needed.

Face Recognition Characteristics in Patients with Age-Related Macular Degeneration Determined Using a Virtual Reality Headset with Eye Tracking.

BACKGROUND AND OBJECTIVES: Face recognition is one of the most serious disabilities of patients with age-related macular degeneration (AMD). Our purpose was to study face recognition using a novel method incorporating virtual reality (VR) and eye tracking. MATERIALS AND METHODS: Eighteen patients with AMD (seven male; median age 83 years; 89% with bilateral advanced AMD) and nineteen healthy controls (five male; median age 68 years) underwent the face recognition test IC FACES (Synthesius, Ljubljna, Slovenia) on a VR headset with built-in eye tracking sensors. Analysis included recognition accuracy, recognition time and fixation patterns. Additionally, a screening test for dementia and imaging with fundus autofluorescence and optical coherence tomography was performed. RESULTS: AMD patients had significantly lower face recognition accuracy (42% vs. 92%; p < 0.001) and longer recognition time (median 4.0 vs. 2.0 s; p < 0.001) in comparison to controls. Both parameters were significantly worse in patients with lower visual acuity. In both groups, eye-tracking data revealed the two classical characteristics of the face recognition process, i.e., fixations clustering mainly in the nose-eyes-mouth triangle and starting observation in the nasal area. CONCLUSIONS: The study demonstrates usability of a VR headset with eye tracking for studying visual perception in real-world situations which could be applicable in the design of clinical studies.

Retinal blood vessel diameters in children and adults exposed to a simulated altitude of 3,000 m.

Introduction: Technological advances have made high-altitude ski slopes easily accessible to skiers of all ages. However, research on the effects of hypoxia experienced during excursions to such altitudes on physiological systems, including the ocular system, in children is scarce. Retinal vessels are embryologically of the same origin as vessels in the brain, and have similar anatomical and physiological characteristics. Thus, any hypoxia-related changes in the morphology of the former may reflect the status of the latter. Objective: To compare the effect of one-day hypoxic exposure, equivalent to the elevation of high-altitude ski resorts in North America and Europe (∼3,000 m), on retinal vessel diameter between adults and children. Methods: 11 adults (age: 40.1 ± 4.1 years) and 8 children (age: 9.3 ± 1.3 years) took part in the study. They spent 3 days at the Olympic Sports Centre Planica (Slovenia; altitude: 940 m). During days 1 and 2 they were exposed to normoxia (FiO2 = 0.209), and day 3 to normobaric hypoxia (FiO2 = 0.162 ± 0.03). Digital high-resolution retinal fundus photographs were obtained in normoxia (Day 2) and hypoxia (Day 3). Central retinal arteriolar equivalent (CRAE) and venular equivalents (CRVE) were determined using an Automated Retinal Image Analyser. Results: Central retinal arteriolar and venular equivalents increased with hypoxia in children (central retinal arteriolar equivalent: 105.32 ± 7.72 µm, hypoxia: 110.13 ± 7.16 µm, central retinal venular equivalent: normoxia: 123.39 ± 8.34 µm, hypoxia: 130.11 ± 8.54 µm) and adults (central retinal arteriolar equivalent: normoxia: 105.35 ± 10.67 µm, hypoxia: 110.77 ± 8.36 µm; central retinal venular equivalent: normoxia: 126.89 ± 7.24 µm, hypoxia: 132.03 ± 9.72 µm), with no main effect of group or group*condition interaction. A main effect of condition on central retinal arteriolar and venular equivalents was observed (central retinal arteriolar equivalent:normoxia: 105.34 ± 9.30 µm, hypoxia: 110.50 ± 7.67 µm, p < 0.001; central retinal venular equivalent: normoxia: 125.41 ± 7.70 µm, hypoxia: 131.22 ± 9.05 µm, p < 0.001). Conclusion: A 20-hour hypoxic exposure significantly increased central retinal arteriolar and venular equivalents in adults and children. These hypoxia-induced increases were not significantly different between the age groups, confirming that vasomotor sensitivity of the retinal vessels to acute hypoxia is comparable between adults and prepubertal children.

The Comparison of Retinal Microvascular Findings in Acute COVID-19 and 1-Year after Hospital Discharge Assessed with Multimodal Imaging-A Prospective Longitudinal Cohort Study.

This study aimed to quantify possible long-term impairment of the retinal microcirculation and microvasculature by reassessing a cohort of patients with acute COVID-19 without other known comorbidities one year after their discharge from the hospital. Thirty patients in the acute phase of COVID-19 without known systemic comorbidities were enrolled in this prospective longitudinal cohort study. Fundus photography, SS-OCT, and SS-OCTA using swept-source OCT (SS-OCT, Topcon DRI OCT Triton; Topcon Corp., Tokyo, Japan) were performed in the COVID-19 unit and 1-year after hospital discharge. The cohort's median age was 60 years (range 28-65) and 18 (60%) were male. Mean vein diameter (MVD) significantly decreased over time, from 134.8 µm in the acute phase to 112.4 µm at a 1-year follow-up (p < 0.001). A significantly reduced retinal nerve fiber layer (RNFL) thickness was observed at follow-up in the inferior quadrant of the inner ring (mean diff. 0.80 95% CI 0.01-1.60, p = 0.047) and inferior (mean diff. 1.56 95% CI 0.50-2.61, p < 0.001), nasal (mean diff. 2.21 95% CI 1.16-3.27, p < 0.001), and superior (mean diff. 1.69 95% CI 0.63-2.74, p < 0.001) quadrants of the outer ring. There were no statistically significant differences between the groups regarding vessel density of the superior and deep capillary plexuses. The transient dilatation of the retinal vessels in the acute phase of COVID-19, as well as RNFL thickness changes, could become a biomarker of angiopathy in patients with severe COVID-19.

The impact of acute COVID-19 on the retinal microvasculature assessed with multimodal imaging.

PURPOSE: To quantify retinal microvascular findings in the acute phase of COVID-19 using multimodal imaging and compare them with healthy, age-matched controls. METHODS: Hospitalized patients in the acute phase of COVID-19 without known systemic comorbidities (n = 75) and healthy controls (n = 101) aged 18-65 were enrolled in this prospective cross-sectional study. The retinal microcirculation and microvasculature impairments were assessed using fundus photography, swept-source optical coherence tomography, and swept-source optical coherence tomography angiography in the COVID-19 unit and compared with healthy, age-matched controls. RESULTS: Retinal findings were predominately observed in patients with severe disease (P = 0.006). Patients with severe disease were shown to have increased both mean vein diameter (Coef. = 19.28, 95% CI: 7.34-31.23, P = 0.002) and mean artery diameter (Coef. = 11.07, 95% CI: 0.84-21.67, P = 0.044). Neither blood vessel diameters were correlated with any confounding variables (age, sex, treatment with oxygen, LDH, or ferritin). Patients with severe COVID-19 were shown to have significantly increased retinal nerve fiber layer thickness in the superior and inferior quadrants both in the inner (S: P = 0.046; I: P = 0.016) and outer (S: P = 0.026; I: P = 0.014) ring and significantly increased GCL thickness in the outer temporal quadrant (P = 0.038). There were no statistically significant differences in vessel density or the foveal avascular zone area between the groups. CONCLUSION: The severity of COVID-19 was significantly correlated with the presence of retinal microangiopathy, which could become a biomarker of angiopathy in patients with COVID-19.

Biomarkers predicting central serous chorioretinopathy episode persistence.

PURPOSE: The purpose of this study was to identify biomarkers at presentation that are associated with a persistent central serous chorioretinopathy (CSC) episode. METHODS: The prospective study included 35 patients with an acute CSC episode. Potential clinical and imaging biomarkers were evaluated at baseline and 3 months from the episode onset. As biomarkers age, sex, steroid use, episode recurrence, central retinal thickness (CRT), macular volume (MV), choroidal thickness (CT), pigment epithelial detachment (PED) height, and width, number of retinal hyperreflective foci (HF), leakage pattern, and area of retinal pigment epithelial (RPE) alterations were investigated. RESULTS: At 3 months from the CSC episode onset, spontaneous resolution occurred in 19 patients, while 16 patients had a persistent CSC episode. The group of patients with a persistent episode was statistically significantly associated with female sex (p = 0.032), older age (p = 0.015), wider PED (p = 0.005), and higher number of HF (p = 0.02). Moreover, this group of patients had a significant association with thinner choroid and diffuse RPE alterations as a pair (p = 0.008). CONCLUSIONS: Older and female CSC patients with wider PED, increased number of HF, thinner choroid, and diffuse RPE alterations at presentation are inclined to episode persistence and could benefit from earlier treatment.

Morphological parameters predicting subthreshold micropulse laser effectiveness in central serous chorioretinopathy.

PURPOSE: The purpose of this prospective study was to predict the effectiveness of subthreshold micropulse laser (SML) based on morphological parameters in patients with central serous chorioretinopathy (CSC). METHODS: Thirty-one patients were examined at presentation, 3 months, and 6 months after the disease onset. In patients with persistent subretinal fluid (SRF) at 3 months, SML was performed. The following morphological parameters were observed just before treatment: central retinal thickness (CRT), maximal SRF, choroidal thickness (CT), pigment epithelial detachment (PED) height and width, number of hyperreflective foci (HF) at fovea and leakage site, secondary choroidal neovascularization (CNV), and severity of retinal pigment epithelium (RPE) alterations using multimodal imaging. RESULTS: Good response was associated with lower SRF (p = 0.038), narrower PED (p = 0.078), and decreasing number of HF at fovea (difHFf) (p = 0 .016) just before the treatment. From a bivariate and multivariate point of view, the two groups differed significantly in the pair (SRF, PED width) (p = 0.048) and in the triple (SRF, PED width, difHFf) (p = 0.026). CONCLUSION: Lower SRF, narrower PED, and decreasing HF could be associated with good response to SML in CSC patients.

Intravitreal bevacizumab treatment for exudative choroidal neovascularisation in best vitelliform macular dystrophy.

PURPOSE: To describe results of intravitreal bevacizumab treatment of the secondary choroidal neovascularisation in Best vitelliform macular dystrophy in an adult and paediatric patient, and present the management of three asymptomatic patients with confirmed BEST1 gene mutation. CASE SERIES DESCRIPTION: Five patients from the same family with the Best vitelliform macular dystrophy are presented. In two patients (aged 63 and 4 years) secondary choroidal neovascularisation caused a rapid decline in visual acuity. In the adult patient with advanced Best vitelliform macular dystrophy, visual acuity did not improve despite eight intravitreal bevacizumab injections to the right eye. The formation of a central scar and rapid reoccurrence of choroidal neovascularisation three months after completing the initial treatment affected the outcome. As for the paediatric patient with bilateral choroidal neovascularisation in the vitelliform stage of Best vitelliform macular dystrophy, a complete recovery of visual acuity was observed after two (left eye) and three (right eye) bevacizumab injections, with adjunctive amblyopia treatment. The other three patients with an abnormal electrooculogram reported no visual problems during more than 10 years of follow-up. Minimal changes were seen on optical coherence tomography in the youngest patient. CONCLUSIONS: Intravitreal bevacizumab seems to be an effective treatment for exudative choroidal neovascularisation in the vitelliform stage of Best vitelliform macular dystrophy; however, it may not be beneficial in the advanced stages of Best vitelliform macular dystrophy. It is important to regularly screen all family members with an abnormal electrooculogram and confirmed mutation for vitelliform changes and choroidal neovascularisation from an early age. The decision for anti-vascular endothelial growth factor treatment should be made on a case-to-case basis as complications may arise.

Intraocular pressure during handgrip exercise: The effect of posture and hypercapnia in young males.

PURPOSE: As part of our investigations of intraocular pressure (IOP) as a potential contributing factor to the spaceflight-associated neuro-ocular syndrome using the 6° head-down tilt (6°HDT) bed rest experimental model, we compared the effect of rest and isometric exercise in prone and supine 6°HDT positions on IOP with that observed in the seated position. METHODS: Ten male volunteers (age = 22.5 ± 3.1 yrs) participated in six interventions. All trials comprised a 10-min rest period, a 3-min isometric handgrip exercise at 30% of participant's maximum, and a 10-min recovery period. The trials were conducted under normocapnic (NCAP) or hypercapnic (FI CO2  = 0.01; HCAP) conditions, the latter mimicking the ambient conditions on the International Space Station. IOP, systolic and diastolic pressures, and heart rate (HR) were measured during the trials. RESULTS: Isometric exercise-induced elevations in HR and mean arterial blood pressure. IOP in the prone 6°HDT position was significantly higher (p < 0.001) compared to IOP in supine 6°HDT position and seated trials at all time points. IOP increased with exercise only in a seated HCAP trial (p = 0.042). No difference was observed between trials in NCAP and HCAP. IOP in the prone 6°HDT position was constantly elevated above 21 mmHg, the lower limit for clinical ocular hypertension. CONCLUSIONS: IOP in the prone 6°HDT position was similar to IOP reported in astronauts upon entering microgravity, potentially indicating that prone, rather than supine 6°HDT position might be a more suitable experimental analog for investigating the acute ocular changes that occur in microgravity.

An Update on COVID-19 Related Ophthalmic Manifestations.

Purpose: To summarize ophthalmic manifestations of coronavirus disease (COVID-19) reported in the literature thus far.Methods: The PubMed database was systematically searched through October 24, 2020, to identify relevant articles using the following search terms: ("COVID-19" OR "SARS-CoV-2") AND ("eye" OR "ophthalmology" OR "retina" OR "retinal findings" OR "cornea" OR "conjunctiva"). Only articles published in English were included in this review.Results: The reported prevalence of ophthalmic manifestations is generally low, but correlates positively with the severity of the disease. Most commonly reported ocular manifestations are conjunctivitis, conjunctival hyperemia and chemosis. Retinal findings include microhemorrhages and flame-shaped hemorrhages, cotton wool spots, dilated veins, and tortuous vessels.Conclusion: Considering the COVID-19 cases have reached pandemic dimensions and are surging, yet again, it is of utmost importance to determine its ophthalmic manifestations and prevent their vision threatening complications. Further studies are warranted to establish whether the retinal findings appear due to the COVID-19 or are an incidental finding in patients with a preexisting diabetic or hypertensive retinopathy.

The eye in extreme environments.

NEW FINDINGS: What is the topic of this review? This review describes the effect of extreme environments on the visual system. What advances does it highlight? The review highlights the way in which environmental stressors affect the eye and vision, both directly and indirectly. ABSTRACT: Much is known about the physiology and anatomy of the eye. Much less is known about the impact of different environments on the eye, and yet it is the pathophysiology that results from this interaction that is often the precursor to disaster. The present review focuses on the effect of different extreme environments on the visual system; in particular, the way in which such environments affect the sensory mechanism of that system.

Hypercapnia augments resistive exercise-induced elevations in intraocular pressure in older individuals.

NEW FINDINGS: What is the central question of this study? Astronauts on-board the International Space Station (ISS) perform daily exercises designed to prevent muscle atrophy and bone demineralization: what is the effect of resistive exercise performed by subjects while exposed to the same level of hypercapnia as on the ISS on intraocular pressure (IOP)? What is the main finding and its importance? The static exercise-induced elevation in IOP during 6° prone head-down tilt (simulating the headward shift of body fluids in microgravity) is augmented by hypercapnia and exceeds the ocular hypertension threshold. ABSTRACT: The present study assessed the effect of 6° head-down (establishing the cephalad fluid displacement noted in astronauts in microgravity) prone (simulating the effect on the eye) tilt during rest and exercise (simulating exercise performed by astronauts to mitigate the sarcopenia induced by unloading of weight-bearing limbs), in normocapnic and hypercapnic conditions (the latter simulating conditions on the International Space Station) on intraocular pressure (IOP). Volunteers (mean age = 57.8 ± 6 years, n = 10) participated in two experimental sessions, each comprising: (i) 10 min rest, (ii) 3 min static handgrip exercise (30% max), and (iii) 2 min recovery, inspiring either room air (NCAP) or a hypercapnic mixture (1% CO2 , HCAP). We measured IOP in the right eye, cardiac output (CO), stroke volume (SV), heart rate (HR) and mean arterial pressure (MAP) at regular intervals. Baseline IOP in the upright seated position while breathing room air was 14.1 ± 2.9 mmHg. Prone 6° head-down tilt significantly (P < 0.01) elevated IOP in all three phases of the NCAP (rest: 27.0 ± 3.7 mmHg; exercise: 32.2 ± 4.8 mmHg; recovery: 27.4 ± 4.0 mmHg) and HCAP (rest: 27.3 ± 4.3 mmHg; exercise: 34.2 ± 6.0 mmHg; recovery: 29.1 ± 5.8 mmHg) trials, with hypercapnia augmenting the exercise-induced elevation in IOP (P < 0.01). CO, SV, HR and MAP were significantly increased during handgrip dynamometry, but there was no effect of hypercapnia. The observed IOP measured during prone 6° HDT in all phases of the NCAP and HCAP trials exceeded the threshold pressure defining ocular hypertension. The exercise-induced increase in IOP is exacerbated by hypercapnia.

Electrophysiological and SD-OCT findings in patients receiving chloroquine therapy in relation to cumulative dosage and duration of treatment.

PURPOSE: Assessment of multifocal ERG (mfERG) changes in patients treated with chloroquine and their correlation with morphological abnormalities, detected by spectral-domain optical coherence tomography in relation to cumulative dosage. METHODS: Data from 37 eyes of 20 patients were retrospectively collected, and one randomly selected eye per patient was considered for statistical analysis. Eyes were divided into three groups according to mfERG and visual acuity findings: normal, early and advanced maculopathy. Functional measures of the first three mfERG rings were compared with retinal thickness measures of the corresponding OCT ETDRS circles. Data on cumulative dose and duration of therapy were also evaluated. RESULTS: The mean mfERG values progressively decreased according to the stage of the disease. In particular in the early maculopathy group, amplitudes were significantly reduced in all the three central rings. The mean ring ratio R1/R2 was abnormal only in the early maculopathy group. OCT thickness measures were significantly lower in all the three ETDRS circles in the advanced maculopathy group, and in the paracentral circle in the early maculopathy group. Considering all the eyes, there was a statistically significant correlation between functional and morphological values (p < 0.001). High chloroquine cumulative dosages were always associated with retinal toxic effects, whereas lower cumulative dosages generated different levels of toxicity. CONCLUSIONS: This study shows a strong association between mfERG ring values and the corresponding OCT thickness measures; however, mfERG may enhance early detection of functional changes in patients treated with chloroquine, especially in ambiguous cases. At low chloroquine cumulative dosages, different subjects might have different susceptibilities to the drug.

Muscle Oxygenation During Hypoxic Exercise in Children and Adults.

INTRODUCTION: While hypoxia is known to decrease peak oxygen uptake ( V . ⁢ o 2 max) and maximal power output in both adults and children its influence on submaximal exercise cardiorespiratory and, especially, muscle oxygenation responses remains unclear. METHODS: Eight pre-pubertal boys (age = 8 ± 2 years.; body mass (BM) = 29 ± 7 kg) and seven adult males (age = 39 ± 4 years.; BM = 80 ± 8 kg) underwent graded exercise tests in both normoxic (PiO2 = 134 ± 0.4 mmHg) and hypoxic (PiO2 = 105 ± 0.6 mmHg) condition. Continuous breath-by-breath gas exchange and near infrared spectroscopy measurements, to assess the vastus lateralis oxygenation, were performed during both tests. The gas exchange threshold (GET) and muscle oxygenation thresholds were subsequently determined for both groups in both conditions. RESULTS: In both groups, hypoxia did not significantly alter either GET or the corresponding V . ⁢ o 2 at GET. In adults, higher V . E levels were observed in hypoxia (45 ± 6 l/min) compared to normoxia (36 ± 6 l/min, p < 0.05) at intensities above GET. In contrast, in children both the hypoxic V . E and V . ⁢ o 2 responses were significantly greater than those observed in normoxia only at intensities below GET (p < 0.01 for V . E and p < 0.05 for V . ⁢ o 2). Higher exercise-related heart rate (HR) levels in hypoxia, compared to normoxia, were only noted in adults (p < 0.01). Interestingly, hypoxia per se did not influence the muscle oxygenation thresholds during exercise in neither group. However, and in contrast to adults, the children exhibited significantly higher total hemoglobin concentration during hypoxic as compared to normoxic exercise (tHb) at lower exercise intensities (30 and 60 W, p = 0.01). CONCLUSION: These results suggest that in adults, hypoxia augments exercise ventilation at intensities above GET and might also maintain muscle blood oxygenation via increased HR. On the other hand, children exhibit a greater change of muscle blood perfusion, oxygen uptake as well as ventilation at exercise intensities below GET.

The Burden of Macular Diseases in Central and Eastern Europe-Implications for Healthcare Systems.

BACKGROUND: Despite the significant impact of retinal diseases such as wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), there is a limited understanding of how these conditions are managed in Central and Eastern Europe (CEE). OBJECTIVES: To provide a comprehensive overview of the clinical and economic burden of wAMD and DME in CEE and the status quo associated with their management. METHODS: A narrative literature review was undertaken to identify existing data on wAMD and DME, including epidemiology, economic burden, clinical guidelines, and available and reimbursed treatments. Data were collected from relevant sources such as PubMed, ophthalmology associations, national statistical offices, and government agency websites; practical viewpoints were provided by local ophthalmologists and healthcare economics experts in CEE. RESULTS: Epidemiological data on wAMD and DME are limited in CEE, and intercountry comparison is difficult because of differences in data collection methodologies. There are effective treatment options for wAMD and DME, and international guidelines advocate the use of intravitreal anti-vascular endothelial growth factor injections as first-line therapy. Local expert organizations broadly support these recommendations; nevertheless, no clinical practice guidelines exist on the treatment of wAMD and DME in CEE. Access to and reimbursement of anti-vascular endothelial growth factor agents vary significantly in the region and, as a result, many patients remain untreated or inadequately treated. CONCLUSIONS: There is an urgent need for the creation of a wAMD/DME treatment program in CEE to ensure that patients have timely access to the most appropriate treatments.

Treat-and-extend therapy using intravitreal aflibercept for neovascular age-related macular degeneration: 2-year real-world practice data from Slovenia.

BACKGROUND: To assess visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD) who initiated intravitreal aflibercept therapy under a treat-and-extend (TE) regimen in real-world settings. METHODS: In this retrospective, observational, multicentre study in Slovenia, medical records of all treatment-naïve patients with nAMD who started intravitreal aflibercept therapy between October 2013 and April 2015 were reviewed. The primary outcome measure was change in mean visual acuity (VA) from baseline to 24 months in patients who received the TE regimen for 2 years, assessed by standardised Early Treatment Diabetic Retinopathy Study charts and calculated as least-squares means. Other outcome measures included the numbers of injections and visits at 12 months and 24 months. RESULTS: The primary analysis included 115 eyes of 105 patients who received TE treatment for 2 years (Group A). The mean VA improved from 57.9 ± 14.9 letters at baseline to 64.6 ± 15.8 letters (+ 6.5 letters, p < 0.0001) at 12 months and 64.8 ± 15.6 letters (+ 7.0 letters, p < 0.0001) at 24 months. The mean number of injections per eye was 8.4 ± 1.9 and the mean number of visits was 8.8 ± 1.7 at 12 months; these numbers decreased to 6.1 ± 2.0 and 6.4 ± 1.9, respectively, at 24 months. The additional analysis included 33 eyes of 33 patients who received TE treatment in Year 1, followed by pro re nata treatment in Year 2 (Group B). Compared with Group A whose vision improvement was maintained at 24 months, the VA gain in Group B eyes seen at 12 months (change in mean VA vs baseline: + 6.9 letters, p = 0.0008) was no longer present at 24 months (change in mean VA vs baseline: + 1.2 letters, p = 0.5733). CONCLUSIONS: Using the TE regimen in clinical practice, intravitreal aflibercept significantly improved visual outcomes in treatment-naïve patients with nAMD, which were maintained over time. TE therapy with intravitreal aflibercept is a rational long-term strategy that can produce favourable outcomes in clinical practice.

Outcome of 5-Year Treatment of Neovascular Age-Related Macular Degeneration With Intravitreal Anti-VEGF Using "Treat and Extend" Regimen.

OBJECTIVE: The aim of this study is twofold. First, to evaluate the long-term outcome of anti-vascular endothelial growth factor (anti-VEGF) treatment in a clinical setting using the "treat-and-extend regimen" (TER) in patients with neovascular age-related macular degeneration (nAMD). Second, to determine the proportion of patients treated with anti-VEGF with good visual acuity (VA), i.e., vision sufficient to maintain a high level of independence. DESIGN: We conducted a single center retrospective review of patients with treatment-naive nAMD who were treated with anti-VEGF. Patients were treated with anti-VEGF intravitreal injections according to the TER. Patients started treatment with monthly injections of either bevacizumab (1.25 mg/0.05 mL) or ranibizumab (0.5 mg/0.05 mL) until there were no signs present of choroidal neovascularization (CNV) activity. CNV activity was determined from fundus examination and SD-OCT imaging. Follow-up administration of intravitreal injections was extended by 2-week intervals, up to a total of 14 weeks, provided no signs of CNV activity were detected. In some patients, the first treatment was replaced with aflibercept (2 mg/0.05 mL). PARTICIPANTS: On the basis of the inclusion criterion for the study, that patients had to be treated for 5 years, a total of 101 patients were included in the study. In all patients, one eye was treated for a 5-year period, and thus we studied 101 eyes. MEASUREMENTS: Best corrected VA was analyzed at baseline and each year during the 5-year follow-up. RESULTS: VA improved initially after year 1 of the treatment. VA decreased in the subsequent 4 years of treatment, but remained significantly higher from year 1 to year 3 of the treatment compared to baseline values. Patients with good VA followed a similar trend: the proportion increased in the first year, and thereafter gradually decreased during the course of the 5-year follow up. At year 5, the number of patients with good VA decreased to baseline values. CONCLUSION: TER with anti-VEGF for nAMD treatment prevents long-term severe visual loss in real-world setting and maintains patients' VA at levels sufficient to ensure independence.

Persistent Placoid Maculopathy Complicated by Cerebral Vasculitis.

Persistent placoid maculopathy (PPM) is a bilateral inflammatory chorioretinopathy characterized by long-standing plaque-like macular lesions. No systemic manifestations have been reported to date. We describe a case of PPM complicated by cerebral vasculitis, suggesting that neurological symptoms, including headache, should be enquired about in all PPM subjects.

Cardiorespiratory Responses of Adults and Children during Normoxic and Hypoxic Exercise.

We aimed to elucidate potential differential effects of hypoxia on cardiorespiratory responses during submaximal cycling and simulated skiing exercise between adults and pre-pubertal children. Healthy, low-altitude residents (adults, N=13, Age=40±4yrs.; children, N=13, age=8±2yrs.) were tested in normoxia (Nor: PiO2=134±0.4 mmHg; 940 m) and normobaric hypoxia (Hyp: PiO2=105±0.6 mmHg; ~3 000 m) following an overnight hypoxic acclimation (≥12-hrs). On both days, the participants underwent a graded cycling test and a simulated skiing protocol. Minute ventilation (VE), oxygen uptake (VO2), heart rate (HR) and capillary-oxygen saturation (SpO2) were measured throughout both tests. The cycling data were interpolated for 2 relative workload levels (1 W·kg-1 & 2 W·kg-1). Higher resting HR in hypoxia, compared to normoxia was only noted in children (Nor:78±17; Hyp:89±17 beats·min-1; p<0.05), while SpO2 was significantly lower in hypoxia (Nor:97±1%; Hyp:91±2%; p<0.01) with no between-group differences. The VE, VO2 and HR responses were higher during hypoxic compared to normoxic cycling test in both groups (p<0.05). Except for greater HR during hypoxic compared to normoxic skiing in children (Nor:155±19; Hyp:167±13 (beats·min-1); p<0.05), no other significant between-group differences were noted during the cycling and skiing protocols. In summary, these data suggest similar cardiorespiratory responses to submaximal hypoxic cycling and simulated skiing in adults and children.