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Background: To evaluate the safety of repeated low-level red-light (RLRL) therapy in children, and the dynamic evolution of choroidal and retinal blood flow., Methods: This is a single-centre, randomised, single-blind, parallel-group clinical trial. Seventy myopic children were randomly assigned to either the intervention group [receiving RLRL therapy plus single-vision spectacle (SVS)] or the control group (wearing SVS). Participants underwent comprehensive ophthalmic examinations following their first irradiation, 9 months continuous RLRL therapy and stop of treatment. Quantitative analyses of choroidal and retinal microcirculation were analysed via optical coherence tomography angiography., Results: Over 9 months of treatment, while the RLRL treatment demonstrated significantly less increases in refractive error and axial length compared with the SVS treatment (ps < 0.05), no abnormalities in fundus structure or visual function (mfERG, VEP and microperimetry) were detected (ps > 0.05). A single red-light exposure did not exert a significant influence on choroidal thickness (ps > 0.05). Upon continuous treatment, the RLRL group achieved peak values in these circulations at 9 months (ps < 0.05). Following cessation of exposure, all circulations exhibited a declining trend, reaching similar levels in both groups (ps > 0.05). As the frequency of red-light exposures intensified, there was a consistent surge in these circulations (ps < 0.05)., Conclusions: Nine months of continuous RLRL exposure does not cause toxic side effects on retinal or optic nerve functions, and there is a time-dependent cumulative response in choroidal and retinal circulation., (© 2024 Royal Australian and New Zealand College of Ophthalmologists.)

Hyperbaric oxygen therapy (HBOT) has been used for the past 50 years for conditions such as decompression disease and wound healing. It has promising effects in the treatment of vision-threatening diseases, such as retinal artery occlusion, retinal vein occlusion, diabetic macular edema, and acute optic neuropathy; however, HBOT has not been approved for use in these conditions by regulatory authorities. This paper provides an overview of the theoretical effectiveness and most recent indications for HBOT in ophthalmology. The fundamental aspects of the physiology of choroidal circulation and metabolism are provided together with the clinical aspects that should be accounted for when selecting patients for this therapy. The paper also presents case reports of when HBOT was successfully implemented. The goals of this review were to explore the indications and benefits of HBOT and to evaluate the effectiveness of HBOT as an intervention in treating ophthalmology disorders. Lastly, the paper details the side-effects and discusses the safety issues of HBOT.

We describe an unusual case of ultra wide fluorescein angiography (UWFA) documented peripheral retinal neovascularization (NVE) with delayed vitreous hemorrhage after placement of an encircling scleral buckle (a common procedure for repair of retinal detachment). Anterior segment ischemia is a rare complication after scleral buckle surgery for the treatment of retinal detachment and results from altered choroidal flow through the impingement of the anterior and long posterior ciliary arteries. UWFA performed for the evaluation of vitreous hemorrhage confirmed ischemia anterior to the scleral buckle and consequential NVE. This case represents the utility of UWFA in evaluating and managing this exceptionally rare complication associated with a common procedure in the field of vitreoretinal surgery., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2020.)

Purpose: To investigate the alterations of central choroidal thickness (CCT) and macular choroidal blood flow in patients with hypertensive chorioretinopathy treated with antihypertensive agents., Methods: In retrospective observational case series, ten eyes of 9 patients with hypertensive chorioretinopathy were enrolled (5 men and 4 women; 43.1 ± 19.6 years of age). CCT and mean blur rate (MBR) had been observed during follow-up using enhanced depth imaging optical coherence tomography and laser speckle flowgraphy, respectively., Results: With the medication for hypertension, serous retinal detachment (SRD) disappeared in all the eyes (mean period, 57.8 ± 50.4 days), and the mean blood pressure decreased (122.7 ± 13.0 mmHg and 93.4 ± 13.2 mmHg at the initial visit and at the day of subretinal fluid absorption, respectively; P < 0.01). The mean logMAR value of best corrected visual acuity showed a tendency toward improvement with the resolution of SRD (0.15 ± 0.30 and 0.08 ± 0.28, P = 0.15). The average MBR significantly decreased when SRD was absorbed (11.4 ± 4.5 and 7.7 ± 2.2, P < 0.01). Similarly, the mean values of CCT decreased (473.2 ± 218.0 μm and 325.7 ± 112.0 μm, P < 0.01). The changing rates of CCT and MBR showed a significant positive correlation (P < 0.01, R = 0.88)., Conclusion: The current study demonstrated a novel finding that choroidal blood flow velocity and thickness concurrently increased in the acute phase of hypertensive chorioretinopathy, suggesting the role of choroidal hyperperfusion in the pathogenesis of hypertensive chorioretinopathy.

Purpose: To investigate the topographic relationship between polypoidal choroidal vasculopathy (PCV) growth and choroidal watershed zones (CWZ) by using indocyanine green angiography (ICGA)., Materials and Methods: We evaluated PCV lesions smaller than the CWZ at baseline and followed up more than 6 months. The CWZ was traced in the early phase ICGA at baseline. The vascular lesion of PCV was traced in baseline and follow-up ICGA. These traces were overlapped and topographic relationships between CWZs and PCV growth were evaluated., Results: Among 31 eyes of 31 patients, enlargement of a PCV lesion was observed in 20 patients (64.5%) at mean follow-up of 30.4 months (6-68 months). A topographical relationship between the CWZ and PCV growth was demonstrated in 14 eyes (70.0%), as the shape of the PCV lesion conformed to the boundary of the CWZ, and/or the growth of the branching vascular network was aligned to the direction of the CWZ extension to the periphery. Growth beyond the boundary of the CWZ was noted in 9 eyes (45.0%), however growth area was greater inside the CWZ than outside in all eyes. Of 15 eyes of extrafoveal lesion at baseline, 8 eyes in which the vascular lesion progressed to the fovea had the CWZ involving the fovea, whereas PCV in three eyes with an extrafoveal CWZ remained as a non-subfoveal disease after mean follow-up of 17.0 months (p = 0.019)., Conclusions: A subfoveal CWZ was related to PCV growth to the fovea. Topographical relationships between PCV growth and the CWZ suggest that choroidal circulation is a predisposition for PCV growth.

Transscleral drug delivery may become a safe alternative to the intravitreal injection for chronic retinal diseases such as age-related macular degeneration or diabetic macular edema. However, the drug delivered onto the sclera subjects to vigorous clearance by episcleral and choroidal circulation; in addition, the penetration from episclera to retina needs to overcome counter-directional ocular fluid current driven by intraocular pressure (IOP) as well as unfavorable drug disposition exerted by drug transporters before the drug reach retina. It is imperative to understand these processes and quantitate their influence for efficient designing of a sustained formulation or device to achieve efficient transscleral drug delivery. The current study was focused on the effects of intraocular pressure (IOP) and choroidal circulation on transscleral drug delivery using triamcinolone acetonide (TA) as a model drug. Rabbit eye IOP was modulated through cannulation in ex vivo study or through cryopexy of ciliary body in vivo studies before subtenon TA injection or episcleral TA-film implantation. In a subgroup of the rabbit eyes, localized choroid atrophy was induced by cryopexy before TA-film implantation. Each condition had a concurrent control group. The vitreous TA concentration was quantitated by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS). The vitreous TA concentration was compared between the study and control groups for effect of IOP or choroid circulation. For ex vivo studies, higher IOP was a significant effect against TA penetration from episclera towards vitreous. TA was 8.5±5ng/mL in receptor chamber with a cross pressure of 50mmHg versus 15.9±10ng/mL with the cross pressure of 5mmHg; p=0.001, t-test. A multivariate regression demonstrated each mmHg of IOP increase would result in 3ng/mL lower concentration in the receptor chamber. Similar IOP effect was also identified in a 3-hour study using euthanized rabbit eyes whose IOP was controlled at 10 or 40mmHg by cannulation (3261±1821ng/mL vs. 755±763ng/mL; p=0.013, Wilcoxon test). However, the effect of IOP was not significant in alive animal with the same IOP setting. In vivo chronic study using low IOP (7.7mmHg) versus normal IOP (14.4mmHg), vitreous TA was not statistically significant (154±200ng/mL vs. 80±130ng/mL, p=0.17, Wilcoxon test). However, removing of choroidal circulation by local cryopexy significantly enhanced the TA penetration from episclera to vitreous (mean 163±129.8ng/mL for choroidal cryopexy vs. 81.8±37.2ng/mL for ciliary cryopexy or 75.5±36ng/mL for control group, p=0.007, regression analysis). In conclusion, the effect of IOP on transscleral drug delivery was not a significant effect in alive rabbit eyes; however, choroidal circulation seems to be a significant effect to affect TA penetration from episclera towards retina and vitreous., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Purpose: To assess choroidal inflammation-related circulatory changes associated with the anterior recurrence of Vogt-Koyanagi-Harada (VKH) disease, using indocyanine green angiography (ICGA) and laser speckle flowgraphy (LSFG)., Methods: This retrospective case series included 17 eyes of 11 patients with VKH disease showing recurrent inflammatory findings in the anterior, but not posterior, segment (i.e. anterior recurrence). Indocyanine green angiography (ICGA) and LSFG were performed at the time of recurrence and one month after the initiation of corticosteroid therapy. The number and total area of hypofluorescent dark dots (HDDs) on ICGA were independently counted by three physicians and measured with ImageJ, respectively. Mean blur rate (MBR), a quantitative index of relative blood flow velocity, was calculated via the LSFG Analyzer software., Results: Hypofluorescent dark dots (HDDs) were identified on ICGA in 13 of 17 eyes (76%) with the anterior recurrence of VKH disease. The number and total area of HDDs significantly decreased from 203 ± 101 dots to 59 ± 51 dots and from 48 789 ± 24 251 pixels to 15 664 ± 13 254 pixels, respectively. The change ratio of MBR significantly increased by 17.9 ± 16.3% after the treatment. Importantly, there was no significant association between the change ratios of HDDs and MBR., Conclusions: These findings on LSFG and ICGA clearly demonstrated subclinical involvement as well as post-treatment improvement of choroidal circulation impairment due to granulomatous inflammation in eyes with the anterior recurrence of VKH disease. The present data suggest the validity of using these two examinations, capable of detecting different circulatory changes, in the management of recurrent VKH disease., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Aim: To evaluate the axial length (AXL) in unilateral idiopathic central serous chorioretinopathy (CSC)., Methods: This retrospective case-control study was comprised of a consecutive case series of 35 patients with acute unilateral idiopathic CSC, and age- and sex-matched 50 control eyes. AXL of both eyes of unilateral CSC patients and the control eyes were investigated. AXL was measured by ultrasonic biometry, and the adjusted AXL was calculated for CSC eyes as measured AXL plus differences of foveal thickness between CSC and normal fellow eyes in millimeters. The main outcome measures were comparison of AXL between CSC, fellow and control eyes., Results: The mean age of 35 CSC patients was 45.5y, and 31 males were included. The adjusted AXL of CSC eyes was 23.52 mm, and the AXL of fellow eyes was 23.46 mm, and of control eyes 23.94 mm. The AXL of both CSC and fellow eyes were significantly shorter than control eyes (CSC vs control, P=0.044; fellow vs control, P=0.026). There was no statistically significant difference in AXL between CSC and fellow eyes., Conclusion: In unilateral idiopathic CSC, the AXL of CSC and fellow eyes are shorter than that of control eyes. Short AXL may be related with choroidal circulation abnormality in CSC.

Background: To evaluate changes of choroidal circulation quantitatively using laser speckle flowgraphy in patients with acute zonal occult outer retinopathy., Design: Retrospective observational case series., Participants: Sixteen eyes of 11 acute zonal occult outer retinopathy patients: seven non-treated eyes with good visual acuity and nine systemic corticosteroid-treated eyes with progressive visual acuity loss. Six eyes with thyroid-associated ophthalmopathy receiving systemic corticosteroid therapy served as controls., Methods: The mean blur rate, an index of quantitative relative blood flow velocity, in the affected area was measured by laser speckle flowgraphy. The changes of mean blur rate, best-corrected visual acuity and the average threshold at the affected area on Humphrey perimetry during 24-week follow up were analysed., Main Outcome Measures: Mean blur rate, best-corrected visual acuity, and the average threshold., Results: In non-treated eyes, the average mean blur rate significantly increased at 24 weeks, with a significant increase of the average threshold. In corticosteroid-treated eyes, the mean blur rates at 1, 4, 12 and 24 weeks were significantly higher than the pretreatment value, with significant improvement of best-corrected visual acuity and the average threshold. The increase in mean blur rate at 4 weeks in corticosteroid-treated acute zonal occult outer retinopathy eyes was significantly higher than that in corticosteroid-treated control eyes., Conclusions: In eyes with acute zonal occult outer retinopathy, the mean blur rate at the affected area significantly increases along with improvement of visual functions. These results suggest that impaired choroidal circulation is involved in the pathogenesis of acute zonal occult outer retinopathy., (© 2013 Royal Australian and New Zealand College of Ophthalmologists.)

The hypothesis that heat stress reduces the ocular blood flow response to exhaustive exercise was tested by measuring ocular blood flow, blood pressure, and end- tidal carbon dioxide partial pressure (PETCO2) in 12 healthy males while they performed cycle ergometer exercise at 75% of the maximal heart rate at ambient temperatures of 20°C (control condition) and 35°C (heat condition), until exhaustion. The blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA) and the superior nasal retinal arteriole (SNRA) were recorded at rest and at 6 and 16 min after the start of exercise period and at exhaustion [after 16 ± 2 min (mean ± SE) and 24 ± 3 min of exercise in the heat and control condition, respectively]. The mean arterial pressure at exhaustion was significantly lower in the heat condition than in the control condition at both 16 min and exhaustion. The degree of PETCO2 reduction did not differ significantly between the two thermal conditions at either 16 min or exhaustion. The blood flow velocity in the RCV significantly increased from the resting baseline value at 6 min in both thermal conditions (32 ± 6% and 25 ± 5% at 20°C and 35°C, respectively). However, at 16 min the increase in RCV blood flow velocity had returned to the resting baseline level only in the heat condition. At exhaustion, the blood flows in the STRA and SNRA had decreased significantly from the resting baseline value in the heat condition (STRA: -19 ± 5% and SNRA: -30 ± 6%), and SNRA blood flow was lower than that in the control condition (-14 ± 6% vs -30 ± 6% at 20°C and 35°C, respectively), despite the finding that both thermal conditions induced the same reductions in PETCO2 and vascular conductance. These findings suggested that the heat condition decreases or suppresses ocular blood flow via attenuation of pressor response during exhaustive exercise. Key PointsThe ocular (retinal and choroidal) blood flow response to exhaustive exercise with heat stress is unknown.We hypothesized that the heat stress decreases ocular blood flow response to exhaustive exercise, since cerebral flow, which is regulated similarly to ocular flow, was reported to decrease during heat stress.To test this hypothesis, ocular blood flow was measured during exhaustive exercise at 20°C (control condition) and 35°C (heat condition).At exhaustion in the heat condition, the ocular flow response was suppressed or decreased with an attenuated pressor response.It is suggested that the heat condition decreases or suppresses the ocular blood flow to exhaustive exercise via attenuation of pressor response.

Aim: To describe and analyze the demographic characteristics and to determine the angiographic features of acute central serous chorioretinopathy(CSCR) in an Egyptian population., Methods: A series of consecutive patients presenting with acute idiopathic CSCR to Mansoura Ophthalmology Center Mansoura University who underwent fluorescein angiography (FA) within a 3-year-period (between January 1, 2007 and December 31, 2009) was retrospectively studied. Patient demographics and angiographic features were studied. Results were compared to those of other Western and Asian populations., Results: Fluorescein angiograms of 86 patients were analyzed. 91% were males. The age range of patients was 24 - 49 years, with a mean age of (38±6) years. The right eye was the presenting eye in 47% of patients. Eighty-seven percent of eyes showed delayed choroidal filling. Thirty-five percent of patients had more than one point of leakage. The macula was the most common site of fluorescein leakage seen in 79% of patients. Peripheral leakage was seen in 14% of patients while peripapillary leakage was seen in 12% of patients. The inkblot leakage pattern was found in 53% of patients. The presenting eye had RPE atrophic changes in 84% of cases. The other eye was assessed in 44 patients (51%). Fifty-five percent of them had signs of RPE atrophic changes., Conclusion: In the Egyptian population, CSCR is seen at younger age with higher male-to-female ratio and more frequent smokestack leaks than other populations. Despite younger age group, this series of patient showed higher frequency of bilateral and multifocal disease compared to other studies. Roles of psychological stress and choroidal ischemia in pathogenesis of CSCR need further evaluation.

Purpose: The precise mechanism causing acute macular neuroretinopathy (AMN) is still unknown. A recent report suggested that choroidal circulation impairment correlates with its pathogenesis. We report a rare case with simultaneous onset of AMN and central retinal vein occlusion (CRVO), which is a retinal circulation disorder., Methods: Case report., Results: A 44-year-old woman complained of central visual loss of the left eye for the previous 2 weeks. The patient's visual acuity was 0.5 in the left eye (OS). Fundoscopic examination revealed a wedge-shaped, dark reddish-brown lesion at the macula, and CRVO-like retinal hemorrhages OS. Fluorescein angiography revealed retinal vasculitis and hypofluorescence corresponding to the macular lesion. The patient's scanning laser ophthalmoscopy infrared imaging result led to a diagnosis of AMN. Two weeks after corticosteroid pulse therapy, her visual acuity improved to 1.2 OS, with improvement of macular findings and Humphrey perimetry. When the dose of oral corticosteroid was decreased, the AMN lesion worsened, with recurrence of retinal hemorrhages. Visual functions improved again after an increased dose of corticosteroid., Conclusion: These results suggest that circulatory disorders almost simultaneously occurred in choroidal and retinal vessels, resulting in the onset of both AMN and CRVO.

Purpose: The precise mechanism causing outer retinal damage in acute macular neuroretinopathy (AMN) remains unclear. In this study, choroidal blood flow velocity was quantitatively evaluated using laser speckle flowgraphy (LSFG) in a patient with AMN who received systemic corticosteroid therapy., Methods: Corticosteroids were systemically administrated across 4 months for an AMN patient. LSFG measurements were taken ten consecutive times before treatment and at 1 week and 1, 3, and 10 months after the onset of therapy. The square blur rate, a quantitative index of relative blood flow velocity, was calculated using LSFG in three regions: Square 1, the macular lesion with findings of severe multifocal electroretinography amplitude reduction, and Squares 2 and 3, funduscopically normal-appearing retinal areas with findings of moderate and mild multifocal electroretinography amplitude reduction, respectively., Results: The AMN lesion gradually decreased after treatment and improved results were detected on the Amsler chart, as well as on optical coherence tomography and scanning laser ophthalmoscopy. When the changing rates of the macular flow were compared with the mean square blur rate level before treatment (100%), 14.6%, 24.5%, 12.9%, and 16.3% increases were detected in Square 1 (macular lesion) at 1 week and 1, 3, and 10 months after treatment, respectively. Similarly, in Square 2 (normal-appearing area next to the lesion), 12.6%, 18.6%, 6.7%, and 8.3% increases were also noted at 1 week and 1, 3, and 10 months after treatment, respectively. In Square 3 (normal-appearing area apart from the lesion), 16.0%, 15.1%, 19.1%, and 3.8% increases were measured at 1 week and 1, 3, and 10 months after treatment, respectively., Conclusion: In a patient with AMN, choroidal blood flow velocity at the lesion site, which was examined with LSFG, sequentially increased during systemic corticosteroid therapy, together with improvement of visual function. The present findings suggest that choroidal circulation impairment relates to the pathogenesis of AMN, extending over a wider area in the posterior pole than the site of an AMN lesion per se.