Assessing acute nicotine impact on choroidal thickness: a randomized, double-blinded study comparing smoking cessation aids, including nicotine gum and electronic cigarettes.

PURPOSE: To explore whether differences in choroidal thickness arise from nicotine consumption in healthy young individuals, specifically comparing the effects of nicotine gum to electronic cigarette (vaping), while maintaining a consistent 4 mg nicotine dosage. METHODS: In a randomized double-blinded prospective cross-sectional study, 20 healthy participants (mean age ± standard deviation: 23 ± 2.36 years) were randomly assigned to either the nicotine gum or vaping group. Choroidal thickness (ChT) measurements were conducted using optical coherence tomography (OCT) (Topcon 3D OCT-1 Maestro System) at baseline, 30, and 60 min after ingesting 4 mg of nicotine, with ChT measurements taken from five different horizontal areas. RESULTS: Neither the nicotine delivery method (gum or vaping) demonstrated a statistically significant impact on ChT mean scores among subjects in the five measured areas at baseline, 30, and 60 min (p > 0.05). However, significant differences were observed in ChT mean scores within subjects across the five areas (F (1.83, 72) = 36.43, p < 0.001), regardless of other study factors such as group, time, and visit (p > 0.05). A statistically significant interaction was identified between the factors of area and time concerning participants' ChT mean scores when stratified by the type of smoking (tobacco, vaping, and dual) (p = 0.003). CONCLUSION: The results of this study revealed that nicotine, up to particular concentration of 4 mg, does not have a statistically significant vasoconstrictive effect on choroidal thickness, regardless of the delivery method, within the examined group. These findings offer valuable insights into the relationship between nicotine intake and choroidal dynamics in young adults.

Potential Choroidal Mechanisms Underlying Atropine's Antimyopic and Rebound Effects: A Mediation Analysis in a Randomized Clinical Trial.

Purpose: To investigate whether choroidal vascularity participates in high-dose atropine's antimyopia and rebound mechanisms. Methods: A mediation analysis was embedded within a randomized controlled trial. In total, 207 myopic children were assigned randomly to group A/B. Participants in group A received 1% atropine weekly (phase 1) and 0.01% atropine daily (phase 2) for 6 months each. Those in group B received 0.01% atropine daily for 1 year. Four plausible intervention mediators were assessed: total choroidal area (TCA), luminal area (LA), stromal area (SA), and choroidal vascularity index (CVI). Results: In group A, LA, SA, and TCA increased significantly after receiving 1% atropine for 6 months. The increment diminished after tapering to 0.01% atropine. In group B, those parameters remained stable. TCA mediated approximately one-third of 1% atropine's effect on spherical equivalent progression in both phases. In phase 1, the mediation effect of TCA was shared by LA and SA, while only that of LA remained significant in phase 2. No mediation effect of CVI was found. Conclusions: One percent atropine induced choroidal thickening by increasing both LA and SA, while 0.01% atropine had little choroidal response. The choroidal changes following 1% atropine treatment diminished after switching to 0.01% atropine. TCA, but not CVI, partially explains atropine's antimyopic and myopic-rebound mechanisms. SA may serve as a potential biomarker to predict the postrebound treatment efficacy of high-dose atropine. (ClinicalTrials.gov number, NCT03949101.).

Efecto de la acetazolamida en la vasculatura retiniana y coroidea de la mácula y el disco óptico mediante angiografía OCT / The effect of acetazolamide on the retinal and choroidal vasculature of the macula and the optic disc using OCT angiography

Introducción y objetivos Investigar el efecto de la acetazolamida (AZ) sobre la microvasculatura ocular retiniana y coroidea en la mácula y los capilares peripapilares radiales (CPR) del disco óptico con angiografía-OCT (OCTA). Materiales y métodos Estudio transversal observacional de 9meses de duración. Se reclutaron 45 ojos de 45 participantes sanos que se sometieron a cirugía de cataratas. Se comparó la densidad de vasos (DV) de la retina macular y la coriocapilar (CC) y la DV de la CPR en la zona del disco óptico antes y 60 min después de administrar 250mg de AZ por vía oral. También se midieron la presión intraocular (PIO) y la presión arterial (PA) sistémica antes de cada exploración. Resultado La edad media era de 73,1±6,9 años. La densidad de vasos (DV) en el plexo capilar superficial (PCS) y profundo (PCP) de la retina y la CC en el área macular no mostraron cambios significativos (p>0,5, para todos los parámetros). La DV en los CPR no mostró cambios significativos con la AZ (p>0,5, para todos los parámetros). El grosor foveal y parafoveal aumentó de 248,98 (± 23,89) a 250,33 (± 23,74) y de 311,62 (± 16,53) a 311,98 (± 16,38) (p<0,001 y p=0,046), respectivamente. La PIO disminuyó de 13,2 (± 3,0) mmHg a 11,8 (± 3,2) mmHg (p<0,001), mientras que la PA sistólica y diastólica disminuyó de 144,8 (± 21,8) a 137,7 (± 19,0) y de 80,0 (± 12,7) a 76,2 (± 11,7) (p=0,021 y p=0,030), respectivamente. Conclusiones Las imágenes de OCTA no revelaron cambios significativos en la VD del disco óptico ni en el VD de la retina y la coroides en la mácula con AZ oral una hora después de su administración en participantes por lo demás sanos que se sometieron a cirugía de cataratas (AU)

Introduction and objectives To investigate the effect of acetazolamide (AZ) on the retinal and choroidal ocular microvasculature in the macula and radial peripapillary capillaries (RPC) of the optic disc with OCT Angiography (OCTA). Materials and method Nine-month observational cross-sectional study. Forty-five eyes from 45 healthy participants who underwent cataract surgery were recruited. Macular retina and choriocapillaris vessel density (VD) and RPC VD in the optic disc area were compared before and 60minutes after 250mg acetazolamide per os. Intraocular pressure (IOP) and systemic blood pressure (BP) were also measured before each scan. Result Mean age was 73.1±6.9 years. VDs in the superficial (SCP) and deep (DCP) capillary plexus of the retina and the choriocapillaris (CC) in the macular area showed no significant change (p>0.5, for all parameters). VD in the RPC showed no significant change with AZ (p>0.5, for all parameters). Foveal and parafoveal thickness increased from 248.98 (±23.89) to 250.33 (±23.74) and from 311.62 (±16.53) to 311.98 (±16.38) (p<0.001 and p=0.046), respectively. IOP decreased from 13.2 (±3.0) mmHg to 11.8 (±3.2) mmHg (p<0.001), while systolic and diastolic BP decreased from 144.8 (±21.8) to 137.7 (±19.0) and from 80.0 (±12.7) to 76.2 (±11.7) (p=0.021 and p=0.030), respectively. Conclusion OCTA imaging did not reveal any significant changes in the VD of the optic disc or the retinal and choroidal VD in the macula with oral AZ one hour after its administration in otherwise healthy participants who underwent cataract surgery (AU)

Chronic Systemic Dexamethasone Regulates the Mineralocorticoid/Glucocorticoid Pathways Balance in Rat Ocular Tissues.

Central serous chorioretinopathy (CSCR) is a retinal disease affecting the retinal pigment epithelium (RPE) and the choroid. This is a recognized side-effect of glucocorticoids (GCs), administered through nasal, articular, oral and dermal routes. However, CSCR does not occur after intraocular GCs administration, suggesting that a hypothalamic-pituitary-adrenal axis (HPA) brake could play a role in the mechanistic link between CSCR and GS. The aim of this study was to explore this hypothesis. To induce HPA brake, Lewis rats received a systemic injection of dexamethasone daily for five days. Control rats received saline injections. Baseline levels of corticosterone were measured by Elisa at baseline and at 5 days in the serum and the ocular media and dexamethasone levels were measured at 5 days in the serum and ocular media. The expression of genes encoding glucocorticoid receptor (GR), mineralocorticoid receptors (MR), and the 11 beta hydroxysteroid dehydrogenase (HSD) enzymes 1 and 2 were quantified in the neural retina and in RPE/ choroid. The expression of MR target genes was quantified in the retina (Scnn1A (encoding ENac-α, Kir4.1 and Aqp4) and in the RPE/choroid (Shroom 2, Ngal, Mmp9 and Omg, Ptx3, Plaur and Fosl-1). Only 10% of the corticosterone serum concentration was measured in the ocular media. Corticosterone levels in the serum and in the ocular media dropped after 5 days of dexamethasone systemic treatment, reflecting HPA axis brake. Whilst both GR and MR were downregulated in the retina without MR/GR imbalance, in the RPE/choroid, both MR/GR and 11ß-hsd2/11ß-hsd1 ratio increased, indicating MR pathway activation. MR-target genes were upregulated in the RPE/ choroid but not in the retina. The psychological stress induced by the repeated injection of saline also induced HPA axis brake with a trend towards MR pathway activation in RPE/ choroid. HPA axis brake causes an imbalance of corticoid receptors expression in the RPE/choroid towards overactivation of MR pathway, which could favor the occurrence of CSCR.

Human immunocompetent choroid-on-chip: a novel tool for studying ocular effects of biological drugs.

Disorders of the eye leading to visual impairment are a major issue that affects millions of people. On the other side ocular toxicities were described for e.g. molecularly targeted therapies in oncology and may hamper their development. Current ocular model systems feature a number of limitations affecting human-relevance and availability. To find new options for pharmacological treatment and assess mechanisms of toxicity, hence, novel complex model systems that are human-relevant and readily available are urgently required. Here, we report the development of a human immunocompetent Choroid-on-Chip (CoC), a human cell-based in vitro model of the choroid layer of the eye integrating melanocytes and microvascular endothelial cells, covered by a layer of retinal pigmented epithelial cells. Immunocompetence is achieved by perfusion of peripheral immune cells. We demonstrate controlled immune cell recruitment into the stromal compartments through a vascular monolayer and in vivo-like cytokine release profiles. To investigate applicability for both efficacy testing of immunosuppressive compounds as well as safety profiling of immunoactivating antibodies, we exposed the CoCs to cyclosporine and tested CD3 bispecific antibodies.

Short-term changes in retinal and choroidal relative flow volume after anti-VEGF treatment for neovascular age-related macular degeneration.

The effects of anti-vascular endothelial growth factor (anti-VEGF) agents on the native ocular vasculature are poorly understood. This pilot study aimed to assess short-term changes in retinal and choroidal perfusion after anti-VEGF treatment for neovascular exudative age-related macular degeneration (nAMD) using the relative flow volume (RFV) parameter derived from laser speckle flowgraphy. Ten treatment-naïve nAMD patients underwent measurements of mean, maximum, minimum, and differential RFV within a retinal arteriolar segment and a choroidal vessel segment outside the neovascular area. Measurement of retinal RFV (rRFV), choroidal RFV (cRFV), and subfoveal choroidal thickness (SCT) was repeated 9 and 35 days after a single anti-VEGF injection. The treatment caused a statistically significant decrease in the mean rRFV, mean cRFV, and SCT during the follow-up (p < 0.05). At the intermediate visit, the mean cRFV and SCT were - 17.6% and - 6.4% compared to baseline, respectively. However, at the final measurement, the mean cRFV was not different from the baseline value, which indicated waning of the anti-VEGF effect. In conclusion, a single anti-VEGF injection in treatment-naïve nAMD resulted in a decrease in retinal arteriolar and choroidal perfusion, according to the RFV parameter, which is a promising tool to simultaneously assess retinal and choroidal perfusion changes in response to anti-VEGF therapy.

Decreased Choroidal Blood Perfusion Induces Myopia in Guinea Pigs.

Purpose: The development of myopia in guinea pigs can be inhibited by attenuating scleral hypoxia by increasing choroidal blood perfusion (ChBP). In this study, we reduced ChBP through surgical and pharmacological methods to determine the effect on myopia development. We also determined whether ChBP was reduced by quinpirole, a drug that enhances form-deprivation myopia (FDM). Methods: ChBP was reduced in the right eyes of guinea pigs via transection of the temporal ciliary arteries or daily injections of phenylephrine into the inferior peribulbar space for one week during normal ocular growth. Other guinea pigs were subjected to two weeks of monocular FDM-with facemasks, along with daily injections of quinpirole, a dopamine D2 receptor agonist, to enhance the FDM. Changes in refraction, axial length, ChBP, and choroidal thickness (ChT) were measured in both treated and fellow eyes of the treatment and control groups. Scleral hypoxia labeling with pimonidazole adducts and α-smooth muscle actin (α-SMA) protein were also measured. Results: Surgical and pharmacological reduction of ChBP induced myopia development in the treated eyes. These treatments rendered the scleral hypoxia and increased scleral α-SMA expression. Furthermore, quinpirole injections, which increased the magnitude of myopia, augmented the FDM-associated reductions in ChBP and ChT and increased the levels of scleral hypoxia and α-SMA protein. Conclusions: Decreased ChBP in guinea pigs leads to scleral hypoxia and scleral myofibroblast transdifferentiation with increased α-SMA expression, ultimately resulting in myopia development. In future clinical trials, ChBP reduction can serve as a potential biomarker for early detection of myopia development.

Changes in choroidal vascular structure from vitreoretinal lymphoma and the intraocular cytokine level associated with clinical resolution after intravitreal methotrexate treatment.

PURPOSE: To evaluate changes in choroidal vascular structure and aqueous cytokine levels in eyes with vitreoretinal lymphoma (VRL) after intravitreal methotrexate (MTX) treatment. METHODS: In this retrospective study, VRL patients who visited our hospital between October 2018 and July 2020 were reviewed. Aqueous samples were obtained before treatment and at clinical resolution after intravitreal MTX therapy. Interleukin (IL)-6 and IL-10 levels and the IL-10-to-IL-6 ratio were evaluated. Swept-source optical coherence tomographic images were obtained along with the aqueous samples. Subfoveal choroidal thickness (SFCT), total vascular area of the choroid (TCA), stromal area (SA), luminal area (LA), and choroidal vascularity index (CVI) were assessed. RESULTS: Twelve patients were enrolled (female:male-5:7). The mean age (± standard deviation) at diagnosis was 60.9±8.5 years. In the 16 eyes diagnosed with VRL, values of SFCT, TCA, LA, and SA significantly decreased after treatment (all p-values <0.05). Additionally, the aqueous cytokine IL-10 level and IL-10-to-IL-6 ratio were significantly decreased (p = 0.001 and p = 0.003, respectively). The choroidal structure in the non-treated fellow eyes did not show any significant difference. There were no further changes in SFCT, TCA, LA, or CVI that occurred during maintenance therapy. For clinical remission, the patients received 7.7±5.5 intravitreal MTX injections. The required number of injections for clinical remission was positively correlated with best-corrected visual acuity, IL-10, and IL-6 levels in the active phase (p = 0.035, p = 0.009, and p = 0.031, respectively). CONCLUSION: Eyes with active VRL exhibited choroidal thickening with increased vascular and stromal areas that decreased after remission following MTX treatment. Higher aqueous IL-10 and IL-6 levels and lower visual acuity in the active phase may indicate the number of injections required for remission; this should be considered in the treatment of patients with VRL.

Prevention of Choroidal Thinning by 0.01% Atropine Administered 24 h Before Exposure to Hyperopic Blur in Young Myopes.

Purpose: To evaluate the persistence of atropine's effect upon choroidal thickness and ocular biometrics and its interaction with hyperopic blur in a population of young adult myopes. Methods: Twenty young (aged 18-35 years) myopic participants with spherical equivalent refractive error of -0.75 to -6.00 D (mean ± SD -2.85 ± 1.64 D) had subfoveal choroidal thickness (SFCT) measurements derived from scans collected from the right eye only with a SD-OCT instrument (Copernicus SOCT-HR) before, as well as 60 min following the introduction of 3 testing conditions: (1) placebo/hyperopic (-3 D) blur, (2) placebo/hyperopic blur one day after administration of 0.01% atropine, and (3) placebo/no blur. Each combination of blur and pharmacological agent was tested on a separate day at approximately the same time of day between 9 am and 2 pm. Results: Repeated measures ANOVA revealed that hyperopic blur and placebo were associated with a decrease in choroidal thickness (mean change: -10.7 ± 2.7 µm, P < 0.001 after 60 min), whereas administration of 0.01% atropine one day before the introduction of hyperopic blur prevented the thinning of the choroid (mean change of +1.1 ± 3.7 µm after 60 min) compared to baseline (both, P > 0.05). There was also no significant difference between the baseline choroidal thickness measurements for any of the conditions tested. Conclusion: Low dose atropine can inhibit signals associated with hyperopic defocus that cause thinning of the choroid for at least 24 h after initial instillation.

A review of treatment modalities in gyrate atrophy of the choroid and retina (GACR).

Gyrate atrophy of the choroid and retina (GACR) is a rare inborn error of amino acid metabolism caused by bi-allelic variations in OAT. GACR is characterised by vision decline in early life eventually leading to complete blindness, and high plasma ornithine levels. There is no curative treatment for GACR, although several therapeutic modalities aim to slow progression of the disease by targeting different steps within the ornithine pathway. No international treatment protocol is available. We systematically collected all international literature on therapeutic interventions in GACR to provide an overview of published treatment effects. METHODS: Following the PRISMA guidelines, we conducted a systematic review of the English literature until December 22nd 2020. PubMed and Embase databases were searched for studies related to therapeutic interventions in patients with GACR. RESULTS: A total of 33 studies (n = 107 patients) met the inclusion criteria. Most studies were designed as case reports (n = 27) or case series (n = 4). No randomised controlled trials or large cohort studies were found. Treatments applied were protein-restricted diets, pyridoxine supplementation, creatine or creatine precursor supplementation, l-lysine supplementation, and proline supplementation. Protein-restricted diets lowered ornithine levels ranging from 16.0-91.2%. Pyridoxine responsiveness was reported in 30% of included mutations. Lysine supplementation decreased ornithine levels with 21-34%. Quality assessment showed low to moderate quality of the articles. CONCLUSIONS: Based primarily on case reports ornithine levels can be reduced by using a protein restricted diet, pyridoxine supplementation (variation-dependent) and/or lysine supplementation. The lack of pre-defined clinical outcome measures and structural follow-up in all included studies impeded conclusions on clinical effectiveness. Future research should be aimed at 1) Unravelling the OAT biochemical pathway to identify other possible pathologic metabolites besides ornithine, 2) Pre-defining GACR specific clinical outcome measures, and 3) Establishing an international historical cohort.

Changes in choroidal thickness after anti-vascular endothelial growth factor treatment of diabetic macular edema, real-life data, 2-year results.

PURPOSE: To evaluate the effect of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection on central choroidal thickness (CCT), central macular thickness (CMT) and best-corrected visual acuity (BCVA) in diabetic macular edema (DME). METHODS: Retrospective, cohort analysis of 90 eyes of 90 patients receiving anti-VEGF therapy for DME. In patients' records, measurements of CCT, CMT, and BCVA before treatment and at 2 years after treatment were recorded. Using enhanced-depth imaging optical coherence tomography (EDI-OCT) images, choroidal thickness and macular thickness measurements were recorded in the subfoveal area and 1 mm nasal to 1 mm temporal to the central foveal area. The baseline and final CMT and CCT values measured from all three quadrants were analyzed statistically. RESULTS: Mean age of the patients was 59.60 ± 9.78 (range, 40-77) years. Mean baseline nasal-CT 226.4 ± 52.5 µm, central-CT 243.2 ± 51.1 µm and temporal-CT 224.6 ± 47.9 µm. Mean final nasal-CT 220.0 ± 50.2 µm, central-CT 235.3 ± 53.6 µm, temporal-CT 220.5 ± 48.1 µm (p = 0.122, p = 0.056, p = 0.184, respectively). Mean baseline nasal- MT 385.3 ± 67.7, central-MT 345.5 ± 119.7 µm and temporal-MT 365.0 ± 64.9 µm. Mean final nasal-MT 359.6 ± 59.2 µm, central-MT 306.2 ± 98.4 µm and temporal-MT 353.4 ± 63.3 µm (p = 0.001, p = 0.002, p = 0.234, respectively). The BCVA improved from 0.52 ± 0.44 logMAR at baseline to 0.38 ± 0.33 at final (p = 0.002). CONCLUSION: After treatment of diabetic macular edema with intravitreal anti-VEGF injection, CMT and BCVA improved significantly, but CCT did not decrease significantly.

Evaluation of the Effect of a Novel ß3-Adrenergic Agonist on Choroidal Vascularity.

Purpose: To determine the effect of the new ß3-agonist (mirabegron), which is used for overactive bladder (OAB) treatment, on central retinal thickness (CRT) and choroidal vascularity. Material and Methods: The 26 eyes of 26 cases using 50 mg tablet mirabegron once per day for OAB were included in this prospective case control study. The CRT, choroidal thickness (ChT), and choroidal vascularity were measured at baseline, week 1 (W1), month 1 (M1), month 2 (M2), and month 3 (M3). Subfoveal ChT measurement included the total subfoveal choroidal thickness (SFCT), and the small and large choroidal vessel layer (SCVL and LCVL) thickness. The total choroidal area (TCA), lumen area (LA), stromal area (SA), stroma/lumen ratio, and choroidal vascularity index (CVI) were measured with the Image-J software. Results: The largest SFCT increase compared to baseline was at M1 (26.8 ± 40.8 µm, P = 0.001). The subfoveal SCVL thickness showed a significant decrease at M2 and M3 (-6.0 ± 8.9 µm, P = 0.002; -7.8 ± 13.4 µm, P = 0.046, respectively). LCVL thickness showed a significant increase at W1, M1, and M2, with the largest at M1. CVI showed a significant increase at M1, M2, and M3 (P < 0.05 for all). The TCA, LA, and SA showed a significant increasing trend at all follow-up periods. LA/SA decreased at W1 because of stromal expansion but increased at M3 with more prominent vascular dilatation. CRT values showed no significant change. Conclusions: Mirabegron had a significant effect on choroidal thickness. Choroidal vascular response is in the form of narrowing in the choriocapillaris and enlargement in the Haller's layer.

Early Postnatal Oxygen Exposure Predicts Choroidal Thinning in Neonates.

Purpose: To evaluate whether choroidal thickness (CT) using arm-mounted optical coherence tomography (OCT) in infants screened for retinopathy of prematurity (ROP) correlates with oxygen exposure in neonates. Methods: OCT images were obtained in infants screened for ROP in a single level IV neonatal intensive care unit. CT was measured at three different locations: the subfoveal center and 1.5 mm from the fovea center in each direction. Correlation and regression analyses were performed to determine the relationship between clinical factors and CT. Clinical factors included gestational age, birth weight, presence of bronchopulmonary dysplasia (BPD), and fraction of inspired oxygen (FiO2) at defined time points: 30 weeks postmenstrual age (PMA), 36 weeks PMA, and on day of imaging. Results: Mean subfoveal, nasal, and temporal choroidal thicknesses CT (SFCT, NCT, and TCT, respectively) were 228.0 ± 51.4 µm, 179.7 ± 50.3 µm, and 186.4 ± 43.8 µm, respectively. SFCT was found to be significantly thicker than NCT and TCT (P < 0.0001 and P = 0.0002, respectively), but no significant difference was found between NCT and TCT (P = 0.547). Compared with infants without BPD, infants with BPD had thinner SFCT and NCT (P = 0.01 and P = 0.0008, respectively). Birth weight was positively correlated with SFCT (r = 0.39, P = 0.01) and NCT (r = 0.33, P = 0.045) but not TCT. Gestational age and ROP stage were not significantly associated with CT. SFCT was found to be significantly thinner with higher average FiO2 supplementation levels at 30 weeks PMA (r = -0.51, P = 0.01) but not at 36 weeks PMA. Regression analysis revealed that FiO2 at 30 weeks PMA was an independent predictor of SFCT in infants screened for ROP (P = 0.01). Conclusions: Early postnatal exposure (<32 weeks PMA) to higher oxygen supplementation in premature neonates statistically predicts choroidal thinning.

A nonhuman primate model of blue light-induced progressive outer retina degeneration showing brimonidine drug delivery system-mediated cyto- and neuroprotection.

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) characterized by atrophy of the retinal pigment epithelium (RPE), loss of photoreceptors, and disruption of choriocapillaris. Excessive light exposure is toxic to the retina and is a known risk factor for AMD. We first investigated the effects of blue light-induced phototoxicity on RPE and photoreceptors in nonhuman primates (NHPs, a model of progressive retinal degeneration) and then evaluated the potential cyto- and neuroprotective effects of the brimonidine drug delivery system (Brimo DDS). In the first set of experiments related to model development, parafoveal lesions of varying severity were induced using blue light irradiation of the retina of cynomolgus monkeys to evaluate the level of phototoxicity in the RPE and photoreceptors. RPE damage was assessed using fundus autofluorescence imaging to quantify areas of hypofluorescence, while thinning of the outer nuclear layer (ONL, photoreceptor nuclei) was quantified using optical coherence tomography (OCT). Photoreceptor function was assessed using multifocal electroretinography (mfERG). RPE damage progressively increased across all lesion severities from 2 to 12 weeks, as did the extent of ONL thinning. Lesions of high severity continued to show reduction in mfERG amplitude, reaching a statistically significant maximum reduction at 12 weeks. Collectively, the first set of experiments showed that blue light irradiation of the NHP eye resulted in progressive retinal degeneration identified by damage to RPE, ONL thinning, and disrupted photoreceptor function - hallmarks of GA in humans. We then used the model to evaluate the cyto- and neuroprotective effects of Brimo DDS, administered as a therapeutic after allowing the lesions to develop for 5 weeks. Placebo DDS or Brimo DDS were administered intravitreally and a set of untreated animals were used as an additional control. In the placebo DDS group, hypofluorescence area continued to increase from baseline, indicating progressive RPE damage, while progression was significantly slowed in eyes receiving Brimo DDS. Likewise, ONL thinning continued to progress over time in eyes that received the placebo DDS, but was reduced in Brimo DDS-treated eyes. Pharmacologically relevant brimonidine concentrations were sustained in the retina for up to 26 weeks following Brimo DDS administration. In summary, Brimo DDS demonstrated cyto- and neuroprotective effects in a novel NHP GA model of progressive retinal degeneration.

Baseline characteristics of myopic choroidal neovascularization in patients above 50 years old and prognostic factors after intravitreal conbercept treatment.

To investigate the influence of age on the function and morphology of patients with myopic choroidal neovascularization (mCNV) and to evaluate the effect and prognostic factors of recurrence of Conbercept treatment on mCNV patients over 50 years. A total of 64 patients (64 eyes) with mCNV were enrolled in this retrospective study. The differences in baseline best-corrected visual acuity (BCVA) and morphological features on imaging between the younger group (˂ 50 years) and the older group (≥ 50 years) were analyzed. Of all, 21 eyes of 21 mCNV patients aged over 50 years who received Conbercept injection were further analyzed. Between the younger and the older group, significant differences were shown in mean BCVA (0.58 ± 0.28 vs 0.77 ± 0.31), subfoveal choroidal thickness (SFCT) (108.17 ± 78.32 µm vs 54.68 ± 39.03 µm) and frequency of vitreoretinal interface abnormalities (VIA) (2 vs 13), respectively (P < 0.05). After treated with Conbercept, the mean BCVA of 21 older mCNV patients increased from 0.83 ± 0.30 at baseline to 0.49 ± 0.24 at one year. Baseline BCVA, external limiting membrane damage, CNV area and CNV location correlated with the visual acuity at the 1-year follow-up. There were 7 (33.3%) recurrent cases during the follow-up and the risk of recurrence in patients with baseline central macular thickness (CMT) ≥ 262.86 µm was 14 times greater than that of patients with CMT < 262.86 µm. The risk of recurrence increased 1.84 times for every 100-µm increment in the CMT. Patients over 50 years with mCNV had a worse BCVA, thinner choroid, and higher risk of VIA than young mCNV patients. The standard Conbercept treatment strategy was safe and effective in mCNV patients over 50 years. As patients over 50 years with a greater CMT have a high risk of recurrence, more attention should be paid on these patients by following them up closely.

Choroidal vascular changes in acne patients under isotretinoin treatment.

PURPOSE: The aim of this study was to evaluate the potential changes in choroidal vasculature in nodulocystic acne patients under isotretinoin treatment by using choroidal thickness (CT), choroidal vascularity index (CVI), and choriocapillaris (CC) flow area. MATERIALS AND METHODS: This prospective study included nodulocystic acne patients under isotretinoin treatment and healthy controls. All patients underwent enhanced depth imaging-optical coherence tomography (EDI-OCT) imaging to assess the subfoveal CT and submacular CVI, and optical coherence tomography angiography (OCTA) imaging to evaluate the CC flow area. RESULTS: A total of 25 patients with acne and 23 controls were included. The mean duration of the treatment was 7.20 ± 0.79 months and the mean daily isotretinoin dose was 38.7 ± 2.8 mg in the acne group. The mean CT and CVI values were significantly higher in the acne group compared to the control group (p = 0.005 and p = 0.027, respectively). The cumulative isotretinoin dose was positively correlated with subfoveal CT and submacular CVI (r = 0.434, p = 0.015 and r = 0.385, p = 0.033, respectively). Regarding the CC flow area, the values for area with a radius of 1 mm, 2 mm and 3 mm were lower in the acne group than in the control group; however, the difference was not significant (p > 0.05, all values). CONCLUSION: After a mean 7-month course of isotretinoin treatment, subfoveal CT and submacular CVI values were significantly higher in the nodulocyctic acne patients. Whether the choroidal changes are permanent or not should be investigated in future studies.

Choroidal and Retinal Changes After Systemic Adrenaline and Photodynamic Therapy in Non-Human Primates.

Purpose: To determine the tomographic, angiographic, and histologic changes in the choroid and retina of cynomolgus monkeys after systemic adrenaline and verteporfin photodynamic therapy (vPDT). Methods: Six cynomolgus monkeys (12 eyes) were treated with vPDT only (n = 2), adrenaline only for eight weeks (n = 2), adrenaline for eight weeks with vPDT at week 4 (n = 4), and adrenaline for 12 weeks and vPDT at week 8 (n = 4). Spectral-domain optical coherence tomography, angiography, and autofluorescence were performed at baseline and every 14 days thereafter until 28 days after adrenaline therapy or vPDT. Choroid parameters included choroidal thickness (CT) changes and structural changes using semiautomated image binarization. Histology with light and electron microscopy was performed. Results: Adrenaline resulted in subfoveal CT increase at week 4 compared with baseline (3.4%, P = 0.010), with further increase at week 8 (3.9%, P = 0.007). This correlated with choroidal luminal area increase (16.0% at week 8 compared with baseline, P = 0.030). Outer retinal changes included subretinal fluid, ellipsoid zone (EZ) disruption, photoreceptor elongation, and sub/intraretinal bright dots. Hypocyanescent spots surrounded by leakage was observed. Histology showed dilated choroidal vessels, intracytoplasmic vacuoles, and retinal pigment epithelium (RPE) enlarged basal infoldings. The vPDT decreased subfoveal CT at four weeks after vPDT (-7.5%, P = 0.007). This correlated with choroidal stromal area decrease (-18.0%, P < 0.010). Within the treatment spot, there was outer retinal atrophy, EZ disruption, irregular RPE thickening, intense hypoautofluorescence, hyperfluorescence, and hypocyanescence. On histology, there were outer retina, RPE, and choroid changes. Conclusions: Adrenaline induces choroidal vessel dilation and CT increase. The vPDT decreases CT because of a reduction in choroidal stromal component.

Targeting choroidal vascular dysfunction via inhibition of circRNA-FoxO1 for prevention and management of myopic pathology.

Myopia has become a global public health problem due to high prevalence. Although the etiological factors of myopia have been gradually recognized, the underlying mechanism remains largely elusive. Choroidal vascular dysfunction is recognized as a critical vision-threatening complication in myopia. Circular RNAs (circRNAs) are shown as the critical regulators in many biological processes and human diseases. In this study, we investigated the role of circRNAs in choroidal vascular dysfunction in myopia. The level of circFoxO1 was significantly upregulated in myopic choroid. circFoxO1 silencing suppressed choroidal endothelial cell viability, proliferation, migration, and tube formation in vitro and alleviated choroidal vascular dysfunction in vivo and ex vivo. circFoxO1 silencing retarded the progression of myopia as shown by reduced extracellular matrix remodeling and improved refractive error and axial elongation. Mechanistically, circFoxO1 acted as the sponge of miR-145 to sequester and inhibit miR-145 activity, thereby inducing VEGFA or ANGPT2 expression. miR-145 could mimic the effects of circFoxO1 silencing on choroidal endothelial phenotypes. Collectively, intervention of choroidal vascular dysfunction via regulating circFoxO1 level is a potential strategy for the prevention and management of myopia.

Systematic review with network meta-analysis of antivascular endothelial growth factor use in managing polypoidal choroidal vasculopathy.

Polypoidal choroidal vasculopathy (PCV) is a vision-threatening disease common in Asian populations. However, the optimal treatment for PCV remains under debate. We searched the databases with optimal searching strategy. The study included randomized clinical trials and prospective studies that recruited patients with active PCV who had received interventions, including PDT, anti-VEGF, or a combination of PDT and anti-VEGF. The Grading of Recommendations Assessment, Development, and Evaluation methodology was used for rating the quality of evidence. Our study included 11 studies involving 1277 patients. The network meta-analysis of RCTs revealed the anti-VEGF group, early combination group, and late combination group had significant BCVA changes compared with the PDT group. Early combination therapy led to a significant decrease in CRT compared with PDT, anti-VEGF, and late combination therapy. Additionally, the early combination group had a significantly higher complete polyp regression rate than the anti-VEGF group. No significant differences were detected in the analysis of the number of anti-VEGF injections and safety profile. This network meta-analysis revealed that early combination therapy exhibited better efficacy related to anatomical outcomes than other therapies. Nonetheless, no significant differences related to BCVA change could be detected between anti-VEGF and late combination therapy.

UVR-B-induced NKR-1 Expression in Ocular Tissues is blocked by Substance P Receptor Antagonist Fosaprepitant in the Exposed as well as Unexposed Partner Eye.

Purpose: To investigate the effect of NKR-1 antagonists in an established UVR-B-induced cataract mouse model. Furthermore, to examine the expression of pro-inflammatory cytokines/chemokines in mouse eyes following unilateral UVR-B exposure.Methods: Mice received intraperitoneally injections of Fosaprepitant and Spantide I, before and after unilateral exposure to UVR-B. After day 3 and 7 post-exposure, ocular tissues were extracted for the detection of NKR-1 protein level by ELISA.Results: Pretreatment with Fosaprepitant decreases NKR-1 expression in exposed ocular tissues as well as in the unexposed lens epithelium compared to the saline group. Spantide I treatment showed a tendency of NKR-1 overexpression in ocular tissues.Conclusion: The clinically approved NKR-1 receptor antagonist Fosaprepitant decreases NKR-1 protein expression effectively not only in the exposed but also in the unexposed partner eye in a UVR-B irradiation mouse model. No effect was seen on the protein concentration of pro-inflammatory cytokines/chemokines in either eye.