ABSTRACT
Purpose: Few studies have explored choroidal changes after cessation of myopia control. This study evaluated the choroidal thickness (ChT) and choroidal vascularity index (CVI) during and after discontinuing long-term low-concentration atropine eye drops use for myopia control. Methods: Children with progressive myopia (6-16 years; n = 153) were randomized to receive 0.01% atropine eye drops or a placebo (2:1 ratio) instilled daily over 2 years, followed by a 1-year washout (no eye drop use). Optical coherence tomography imaging of the choroid was conducted at the baseline, 2-year (end of treatment phase), and 3-year (end of washout phase) visits. The main outcome measure was the subfoveal ChT. Secondary measures include the CVI. Results: During the treatment phase, the subfoveal choroids in both treatment and control groups thickened by 12-14 µm (group difference P = 0.56). During the washout phase, the subfoveal choroids in the placebo group continued to thicken by 6.6 µm (95% confidence interval [CI] = 1.7 to 11.6), but those in the atropine group did not change (estimate = -0.04 µm; 95% CI = -3.2 to 3.1). Participants with good axial eye growth control had greater choroidal thickening than the fast-progressors during the treatment phase regardless of the treatment group (P < 0.001), but choroidal thickening in the atropine group's fast-progressors was not sustained after stopping eye drops. CVI decreased in both groups during the treatment phase, but increased in the placebo group after treatment cessation. Conclusions: On average, compared to placebo, 0.01% atropine eye drop treatment did not cause a differential rate of change in ChT during treatment, but abrupt cessation of long-term 0.01% atropine eye drops may disrupt normal choroidal thickening in children.
Subject(s)
Atropine , Choroid , Mydriatics , Ophthalmic Solutions , Tomography, Optical Coherence , Humans , Atropine/administration & dosage , Choroid/pathology , Choroid/diagnostic imaging , Choroid/drug effects , Male , Female , Child , Adolescent , Mydriatics/administration & dosage , Myopia/drug therapy , Myopia/physiopathology , Double-Blind Method , Follow-Up Studies , Refraction, Ocular/physiology , Myopia, Degenerative/drug therapy , Myopia, Degenerative/physiopathology , Visual AcuityABSTRACT
Purpose: Intravitreal injection of anti-VEGF antibodies remains the primary therapy for exudative age-related macular degeneration (exAMD), although its efficacy is limited. Previous research has demonstrated that both a loss-of-function mutation of srr and the intravenous injection of a serine racemase inhibitor, L-aspartic acid ß-hydroxamate (L-ABH), significantly inhibit laser-induced choroidal neovascularization (CNV) in mice. Given that L-ABH is a small molecule, this study investigated the effects of L-ABH administered via eye drops on CNV, aiming to develop a noninvasive treatment strategy for exAMD. Methods: CNV models in mice and rhesus macaques were established through laser photocoagulation. Seven monkeys were randomly assigned to receive either saline solution or L-ABH eye drops. Intraperitoneal or intravenous injection of fluorescein characterized CNV in both mice and monkeys. Fluorescein fundus angiography was used to assess leakage, whereas optical coherence tomography measured retinal thickness in the monkeys. Results: L-ABH eye drops significantly reduced fluorescein leakage in laser-injured mice (P < 0.001 compared to saline). In laser-injured rhesus macaques, the average percent changes in leakage areas treated with L-ABH were 2.5% ± 25.8% (P = 0.004) and 1.5% ± 75.7% (P = 0.023 compared to saline solution) on day 14 and day 28, respectively. However, L-ABH eye drops did not significantly affect the number of grade IV laser spots or retinal thickness, whereas bevacizumab did. Conclusions: This study demonstrates the potential efficacy of an SRR inhibitor in two animal models of laser-induced CNV. Translational Relevance: This represents the first investigation into the effects of topical delivery of an SRR inhibitor on CNV.
Subject(s)
Choroidal Neovascularization , Disease Models, Animal , Fluorescein Angiography , Macaca mulatta , Mice, Inbred C57BL , Tomography, Optical Coherence , Animals , Choroidal Neovascularization/drug therapy , Choroidal Neovascularization/pathology , Mice , Racemases and Epimerases/antagonists & inhibitors , Racemases and Epimerases/genetics , Racemases and Epimerases/metabolism , Laser Coagulation/adverse effects , Ophthalmic Solutions , Male , Choroid/drug effects , Choroid/pathology , Choroid/diagnostic imaging , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/administration & dosage , Enzyme Inhibitors/therapeutic use , Hydroxamic Acids/administration & dosage , Hydroxamic Acids/pharmacology , Hydroxamic Acids/therapeutic useABSTRACT
Purpose: Compare choroidal changes in ranibizumab versus panretinal photocoagulation (PRP)-treated eyes with proliferative diabetic retinopathy (PDR). Methods: DRCR Retina Network Protocol S post hoc analysis evaluated optical coherence tomography change in choroidal thickness (subfoveal and 3mm superior and inferior to the fovea) through five years; choroidal vascularity index (CVI) was assessed at baseline and one year. Mixed linear models for choroidal change included adjustments for the baseline choroidal value and age. Results: This study included 328 eyes (158 ranibizumab and 170 PRP) from 256 participants (88 ranibizumab and 95 PRP eyes at five years). Mean change in choroidal thickness from baseline to five years at the fovea was -12 µm in ranibizumab versus -8 µm in PRP (difference [95% confidence interval]: -4 [-18 to 10], P = 0.57), superior was -14 µm versus -19 µm (difference: 5 [-8 to 17], P = 0.45) and inferior was -26 µm versus -32 µm [difference: 5 (-9 to 20), P = 0.45]; change at all three points within the ranibizumab group, and the superior and inferior points for PRP, were statistically significant (P < .05). Mean change in CVI at one year was -0.02% in ranibizumab versus -0.95% in PRP (difference: 0.93 [-0.35 to 2.21], P = 0.14). Conclusions: In patients with PDR, treatment with ranibizumab versus PRP did not result in statistically significant differences in five-year choroidal thickness or one-year CVI change. Both groups had significant decreases in choroidal thickness at five years. Translational Relevance: Ranibizumab treatment for PDR did not statistically significantly affect choroidal thickness or vascularity differently than PRP.
Subject(s)
Angiogenesis Inhibitors , Choroid , Diabetic Retinopathy , Intravitreal Injections , Laser Coagulation , Ranibizumab , Tomography, Optical Coherence , Humans , Ranibizumab/administration & dosage , Ranibizumab/therapeutic use , Tomography, Optical Coherence/methods , Choroid/diagnostic imaging , Choroid/blood supply , Choroid/drug effects , Choroid/pathology , Female , Male , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Middle Aged , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/therapy , Diabetic Retinopathy/diagnostic imaging , Laser Coagulation/methods , Visual Acuity , Aged , Follow-Up Studies , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
The annual increase in myopia prevalence poses a significant economic and health challenge. Our study investigated the effect of calcitriol role in myopia by inducing the condition in guinea pigs through form deprivation for four weeks. Untargeted metabolomics methods were used to analyze the differences in metabolites in the vitreous body, and the expression of vitamin D receptor (VDR) in the retina was detected. Following form deprivation, the guinea pigs received intraperitoneal injections of calcitriol at different concentrations. We assessed myopia progression using diopter measurements and biometric analysis after four weeks. Results indicated that form deprivation led to a pronounced shift towards myopia, characterized by reduced choroidal and scleral thickness, disorganized collagen fibers, and decreased scleral collagen fiber diameter. Notably, a reduction in calcitriol expression in vitreous body, diminished vitamin D and calcitriol levels in the blood, and decreased VDR protein expression in retinal tissues were observed in myopic guinea pigs. Calcitriol administration effectively slowed myopia progression, preserved choroidal and scleral thickness, and prevented the reduction of scleral collagen fiber diameter. Our findings highlight a significant decrease in calcitriol and VDR expressions in myopic guinea pigs and demonstrate that exogenous calcitriol supplementation can halt myopia development, enhancing choroidal and scleral thickness and scleral collagen fiber diameter.
Subject(s)
Calcitriol , Myopia , Retina , Animals , Guinea Pigs , Myopia/metabolism , Myopia/drug therapy , Myopia/pathology , Calcitriol/pharmacology , Retina/metabolism , Retina/drug effects , Retina/pathology , Receptors, Calcitriol/metabolism , Receptors, Calcitriol/genetics , Male , Disease Models, Animal , Sclera/metabolism , Sclera/drug effects , Sclera/pathology , Choroid/metabolism , Choroid/drug effects , Choroid/pathology , Vitamin D/pharmacology , Vitamin D/administration & dosage , Axial Length, Eye , Vitreous Body/metabolism , Vitreous Body/drug effects , Disease Progression , Collagen/metabolismABSTRACT
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.
Subject(s)
Choroid , Electronic Nicotine Delivery Systems , Nicotine , Tomography, Optical Coherence , Humans , Choroid/pathology , Choroid/diagnostic imaging , Choroid/drug effects , Male , Double-Blind Method , Female , Tomography, Optical Coherence/methods , Prospective Studies , Cross-Sectional Studies , Young Adult , Adult , Nicotine/administration & dosage , Nicotine/adverse effects , Smoking Cessation/methods , Tobacco Use Cessation Devices , Nicotine Chewing GumABSTRACT
Aim of this study was to evaluate the efficacy of switching treatment to faricimab in neovascular age-related macular degeneration (nAMD) from other anti-VEGF agents. Fifty-eight eyes of fifty-one patients with nAMD and a full upload series of four faricimab injections were included. Demographic data, multimodal imaging and treatment parameters were recorded. The primary outcome measures were changes in central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). A subgroup analysis was performed for eyes with prior ranibizumab (R) or aflibercept (A) treatment. Mean injection intervals before and after switching were comparable (33.8 ± 11.2 vs. 29.3 ± 2.6 days; p = 0.08). Mean CST of 361.4 ± 108.1 µm prior to switching decreased significantly to 318.3 ± 97.7 µm (p < 0.01) after the third faricimab injection, regardless of prior anti-VEGF treatment (p < 0.01). Although SFCT slightly improved for the whole cohort from 165.8 ± 76.8 µm to 161.0 ± 82,8 µm (p = 0.029), subgroup analysis did not confirm this positive effect (subgroup R: p = 0.604; subgroup A: p = 0.306). In patients with a suboptimal response to aflibercept or ranibizumab in nAMD, farcimab can improve CST and slightly improve or maintain SFCT. Further prospective randomized trials are warranted.
Subject(s)
Angiogenesis Inhibitors , Choroid , Ranibizumab , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Humans , Male , Female , Aged , Ranibizumab/administration & dosage , Ranibizumab/therapeutic use , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Choroid/drug effects , Choroid/diagnostic imaging , Choroid/pathology , Aged, 80 and over , Treatment Outcome , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Receptors, Vascular Endothelial Growth Factor/therapeutic use , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Retina/pathology , Retina/drug effects , Retina/diagnostic imaging , Intravitreal Injections , Macular Degeneration/drug therapy , Macular Degeneration/pathology , Tomography, Optical Coherence , Visual Acuity/drug effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Drug SubstitutionABSTRACT
A-scan ultrasonography enables precise measurement of internal ocular structures. Historically, its use has underpinned fundamental studies of eye development and aberrant eye growth in animal models of myopia; however, the procedure typically requires anaesthesia. Since anaesthesia affects intra-ocular pressure (IOP), we investigated changes in internal ocular structures with isoflurane exposure and compared measurements with those taken in awake animals using optical coherence tomography (OCT). Continuous A-scan ultrasonography was undertaken in tri-coloured guinea pigs aged 21 (n = 5), 90 (n = 5) or 160 (n = 5) days while anaesthetised (up to 36 min) with isoflurane (5% in 1.5L/min O2). Peaks were selected from ultrasound traces corresponding to the boundaries of the cornea, crystalline lens, retina, choroid and sclera. OCT scans (Zeiss Cirrus Photo 800) of the posterior eye layers were taken in 28-day-old animals (n = 19) and compared with ultrasound traces, with choroid and scleral thickness adjusted for the duration of anaesthesia based on the changes modelled in 21-day-old animals. Ultrasound traces recorded sequentially in left and right eyes in 14-day-old animals (n = 30) were compared, with each adjusted for anaesthesia duration. The thickness of the cornea was measured in enucleated eyes (n = 5) using OCT following the application of ultrasound gel (up to 20 min). Retinal thickness was the only ultrasound internal measure unaffected by anaesthesia. All other internal distances rapidly changed and were well fitted by exponential functions (either rise-to-max or decay). After 10 and 20 min of anaesthesia, the thickness of the cornea, crystalline lens and sclera increased by 17.1% and 23.3%, 0.4% and 0.6%, and 5.2% and 6.5% respectively, whilst the anterior chamber, vitreous chamber and choroid decreased by 4.4% and 6.1%, 0.7% and 1.1%, and 10.7% and 11.8% respectively. In enucleated eyes, prolonged contact of the cornea with ultrasound gel resulted in an increase in thickness of 9.3% after 10 min, accounting for approximately half of the expansion observed in live animals. At the back of the eye, ultrasound measurements of the thickness of the retina, choroid and sclera were highly correlated with those from posterior segment OCT images (R2 = 0.92, p = 1.2 × 10-13, R2 = 0.55, p = 4.0 × 10-4, R2 = 0.72, p = 5.0 × 10-6 respectively). Furthermore, ultrasound measures for all ocular components were highly correlated in left and right eyes measured sequentially, when each was adjusted for anaesthetic depth. This study shows that the depth of ocular components can change dramatically with anaesthesia. Researchers should therefore be wary of these concomitant effects and should employ adjustments to better render 'true' values.
Subject(s)
Anesthetics, Inhalation , Isoflurane , Tomography, Optical Coherence , Ultrasonography , Animals , Tomography, Optical Coherence/methods , Guinea Pigs , Isoflurane/pharmacology , Anesthetics, Inhalation/pharmacology , Choroid/drug effects , Choroid/diagnostic imaging , Aging/physiology , Intraocular Pressure/drug effects , Intraocular Pressure/physiology , Cornea/drug effects , Cornea/diagnostic imaging , Retina/drug effects , Retina/diagnostic imaging , Sclera/drug effects , Sclera/diagnostic imaging , Time Factors , Eye/diagnostic imaging , Eye/drug effects , Disease Models, Animal , Lens, Crystalline/diagnostic imaging , Lens, Crystalline/drug effectsABSTRACT
PURPOSE: to analyze the structural changes of choroidal thickness in patients with brolucizumab-related exudative vitritis after intravitreal injection, using EDI-OCT. METHODS: One hundred eyes of one hundred patients, affected by exudative age related-macular degeneration treated with brolucizumab intravitreal injection between January 2022 and august 2023 at Eye clinic of University of Federico II Naples, were enrolled. All eyes underwent macular examination using Enhanced Deep Imaging-OCT (Spectralis, Heidelberg Engineering inc.) preoperatively and at each postoperative check (1, 3, 6, 12 months). Anterior segment evaluation at slit lamp before and after injection was performed. RESULTS: Of the 100 treated eyes, 4 showed inflammatory signs related to exudative vitreitis, with inflammation signs at slit lamp examination and confirmed by OCT and B scan ecography. EDI-OCT revealed, in all of these 4 patients, a significant increase of choroidal thickness compared to baseline. CONCLUSION: choroidal thickness could be correlated in the inflammatory response generated in patients undergoing treatment with brolucizumab.
Subject(s)
Antibodies, Monoclonal, Humanized , Choroid , Intravitreal Injections , Tomography, Optical Coherence , Humans , Male , Female , Choroid/pathology , Choroid/drug effects , Choroid/diagnostic imaging , Tomography, Optical Coherence/methods , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Aged , Wet Macular Degeneration/drug therapy , Aged, 80 and over , Angiogenesis Inhibitors/administration & dosage , Middle AgedABSTRACT
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.).
Subject(s)
Atropine , Choroid , Mediation Analysis , Myopia , Tomography, Optical Coherence , Child , Humans , Atropine/administration & dosage , Choroid/drug effects , Refraction, Ocular , Myopia/prevention & controlABSTRACT
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)
Subject(s)
Humans , Male , Female , Middle Aged , Aged , Aged, 80 and over , Acetazolamide/pharmacology , Carbonic Anhydrase Inhibitors/pharmacology , Retinal Vessels/drug effects , Optic Disk/drug effects , Choroid/drug effects , Cross-Sectional Studies , Tomography, Optical Coherence , Computed Tomography Angiography , Retinal Vessels/diagnostic imaging , Optic Disk/diagnostic imaging , Choroid/diagnostic imagingABSTRACT
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.
Subject(s)
Glucocorticoids/metabolism , Mineralocorticoids/metabolism , Retina/metabolism , Animals , Central Serous Chorioretinopathy/drug therapy , Central Serous Chorioretinopathy/physiopathology , Choroid/drug effects , Choroid/metabolism , Corticosterone/blood , Dexamethasone/metabolism , Dexamethasone/pharmacology , Eye/metabolism , Hypothalamo-Hypophyseal System/metabolism , Ocular Physiological Phenomena/drug effects , Pituitary-Adrenal System/metabolism , Rats , Rats, Inbred Lew , Receptors, Glucocorticoid/metabolism , Retina/drug effects , Retinal Pigment Epithelium/drug effects , Retinal Pigment Epithelium/metabolism , Signal Transduction/genetics , Signal Transduction/physiologyABSTRACT
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.
Subject(s)
Biological Products/pharmacology , Choroid/drug effects , Endothelial Cells/drug effects , Microchip Analytical Procedures , Antibodies, Bispecific/drug effects , Antibodies, Bispecific/metabolism , Humans , Melanocytes/drug effects , Melanocytes/metabolismABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/therapeutic use , Choroid/blood supply , Choroid/drug effects , Macular Degeneration/drug therapy , Macular Degeneration/pathology , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retinal Vessels/drug effects , Aged , Aged, 80 and over , Angiogenesis Inhibitors/pharmacology , Choroid/pathology , Disease Management , Disease Susceptibility , Female , Humans , Macular Degeneration/diagnostic imaging , Male , Treatment OutcomeABSTRACT
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.
Subject(s)
Choroid/blood supply , Myopia/physiopathology , Regional Blood Flow/physiology , Actins/metabolism , Animals , Axial Length, Eye , Blood Flow Velocity , Blotting, Western , Choroid/drug effects , Choroid/pathology , Ciliary Arteries/surgery , Computed Tomography Angiography , Disease Models, Animal , Dopamine Agonists/pharmacology , Electroretinography , Guinea Pigs , Hypoxia/metabolism , Muscle, Smooth/metabolism , Myopia/metabolism , Phenylephrine/pharmacology , Quinpirole/pharmacology , Receptors, Dopamine D2/metabolism , Refraction, Ocular/physiology , Sclera/metabolism , Tomography, Optical CoherenceABSTRACT
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.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Choroid/blood supply , Cytokines/analysis , Lymphoma/drug therapy , Methotrexate/therapeutic use , Retinal Neoplasms/drug therapy , Aged , Antimetabolites, Antineoplastic/administration & dosage , Choroid/drug effects , Choroid/pathology , Female , Humans , Intravitreal Injections , Lymphoma/pathology , Male , Methotrexate/administration & dosage , Middle Aged , Retinal Neoplasms/pathology , Retrospective Studies , Vitreous Body/drug effects , Vitreous Body/pathologyABSTRACT
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.
Subject(s)
Atropine/pharmacology , Atropine/therapeutic use , Choroid/drug effects , Hyperopia/pathology , Myopia/drug therapy , Adult , Dose-Response Relationship, Drug , Female , Humans , Male , White People , Young AdultABSTRACT
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.
Subject(s)
Choroid/drug effects , Gyrate Atrophy/drug therapy , Metabolism, Inborn Errors/drug therapy , Retina/drug effects , Choroid/pathology , Humans , Mutation , Retina/pathologyABSTRACT
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.
Subject(s)
Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/drug therapy , Macular Edema/drug therapy , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Adult , Aged , Choroid/diagnostic imaging , Choroid/drug effects , Choroid/pathology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/pathology , Female , Follow-Up Studies , Humans , Intravitreal Injections , Macula Lutea/diagnostic imaging , Macula Lutea/drug effects , Macula Lutea/pathology , Macular Edema/diagnosis , Macular Edema/etiology , Macular Edema/pathology , Male , Middle Aged , Ranibizumab/administration & dosage , Receptors, Vascular Endothelial Growth Factor/administration & dosage , Recombinant Fusion Proteins/administration & dosage , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Visual AcuityABSTRACT
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.
Subject(s)
Choroid/pathology , Fovea Centralis/pathology , Oxygen/pharmacology , Retinopathy of Prematurity/diagnosis , Tomography, Optical Coherence/methods , Choroid/drug effects , Female , Follow-Up Studies , Fovea Centralis/drug effects , Gestational Age , Humans , Infant, Newborn , Male , Prospective StudiesABSTRACT
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.