Choroidal changes in lens-induced myopia in guinea pigs

The purpose of this study was to study changes in choroidal thickness (ChT) and choroidal blood perfusion (ChBP), and the correlation between them, in guinea pig myopia. The reliability of optical coherence tomography angiography (OCTA) for measuring ChT and ChBP was verified in guinea pigs, after cervical dislocation (n = 7) or temporal ciliary artery transection (n = 6). Changes in refraction, axial length, ChT, and ChBP were measured during spontaneous myopia (n = 9), monocular form-deprivation myopia (FDM, n = 13), or lens-induced myopia (LIM, n = 14), and after 4 days of recovery from FDM and LIM. The abolition (by cervical dislocation) or reduction (by temporal ciliary artery transection) of ChBP, and of the associated changes in ChT, were verified by OCTA, thus validating the method of measurement. In the spontaneous myopia group, ChT and ChBP were reduced by 25.2% and 31.9%, respectively. In FDM eyes, mean ± SD ChT and ChBP decreased significantly compared with the untreated fellow eyes (ChT fellow: 76.13 ± 9.34 μm versus 64.76 ± 11.15 μm for FDM; ChBP fellow: 37.87 ± 6.37 × 103 versus 30.27 ± 6.06 × 103 for FDM) and increased after 4 days of recovery (ChT: 77.94 ± 12.57 μm; ChBP: 37.41 ± 6.11 × 103). Effects of LIM were similar to those of FDM. Interocular differences in ChT and ChBP were significantly correlated in each group (FDM: R = 0.71, P < 0.001; LIM: R = 0.53, P < 0.001). ChT and ChBP were significantly decreased in all three models of guinea pig myopia, and they both increased during recovery. Changes in ChT were positively correlated with changes in ChBP. Therefore, it is possible that the changes of ChT are responsible for the changes of ChBP or vice versa.

To investigate the effects of manual acupuncture (MA) on the signal transduction and activator of transcription (STAT)3 - matrix metalloproteinase (MMP)-2 pathway in a guinea pig model of lens-induced myopia (LIM). A total of 36 male pigmented guinea pigs (aged 2 weeks) were randomly assigned to the normal control (NC) (n = 12), LIM (n = 12) and LIM + MA (n = 12) groups. The NC group received no intervention. To create myopia, the right eyes of the LIM and LIM + MA groups were covered with -6.00 D lenses. The LIM + MA group received 30 min of acupuncture stimulation daily at Taiyang and LI4. The effect of LIM modelling and MA on ocular measurements, expression of STAT3, phosphorylated (p)-STAT3, MMP-2 and tissue inhibitor of MMP-2 (TIMP)-2 expression (as well as histopathology, morphology and immunohistochemistry of the guinea pigs' eyes) were evaluated. Compared with the NC group, the LIM group showed increased expression of STAT3, p-STAT3 and MMP-2, and decreased expression of TIMP-2, as well as an increase in ocular measurements. The eye tissue morphology was disrupted and fibres became thinner in the LIM group. Compared to the LIM group, the LIM + MA group exhibited a noteworthy decline in the expression of STAT3, p-STAT3 and MMP-2, a significant increase in TIMP-2, and a decrease in ocular measurements and tissue morphology, which were similar to that of the NC group. Acupuncture has the potential to decrease STAT3 activation and block the STAT3-MMP-2 pathway in the ocular tissue of guinea pigs with experimental LIM, thereby delaying the development of myopia.

Zonula occludens-1 (ZO-1) and occludin are important tight junction (TJ)-associated proteins, which are expressed in the retinal pigment epithelium (RPE)-choroid complex. Retinoic acid (RA) is a regulator of eye growth and may play an important role in forming functional TJs. The aim of this study was to detect the changes that occur in the expression of ZO-1 and occludin in the RPE-choroid complex of guinea pigs with lens-induced myopia (LIM), and to investigate the effect of RA on TJ-associated proteins in vivo. We developed an animal model of myopia by placing a −6.00 D negative lens on the right eyes of 3-week-old guinea pigs. The refractive error and axial length of the eye were measured on days 0, 3, 7 and 14. High-performance liquid chromatography (HPLC) was performed to detect the changes in endogenous RA in the RPE-choroid complex. The expression of ZO-1 and occludin was observed by immunofluorescence and assayed by western blot analysis. Additionally, 2 μl LE540 (2.5 μg/μl), an antagonist of RA receptors (RARs), was injected into the vitreous chamber of the eyes of guinea pigs with LIM and 2 μl phosphate-buffered saline (PBS) (2.5 μg/μl) were injected as a negative control. We observed no obvious change in RA, ZO-1 and occludin expression in the normal control group within 14 days. In the LIM and LIM plus PBS groups, the level of RA and the expression of ZO-1 and occludin in the RPE-choroid complex significantly increased within 14 days along with the development of myopia. However, the level of RA was inhibited and the expression of TJ-associated proteins decreased in the eyes of guinea pigs with LIM following the injection of LE540. Thus, we consider that the expression of ZO-1 and occludin is increased in the RPE-choroid complex during the development of myopia. This change in expression may be regulated by RA, a factor known to be involved in the regulation of eye growth.

Purpose: To compare the regional differences in the choroidal thickness (CT) between patients with pachychoroid neovasculopathy (PNV) and classic exudative age-related macular degeneration (ceAMD). Materials and Methods: We included both eyes of patients with unilateral macular neovascularization (MNV) due to ceAMD or PNV. Unilateral eyes of normal subjects were also included as a normal control group. The regional difference in CT was defined as a difference between the macular and extramacular areas, and calculated as the ratio of subfoveal CT (SFCT) to nasal peripapillary CT (PCT). Results: In normal subjects, the choroid was 2.25 ± 0.10 times thicker at the macula than at the extramacular area. The SFCT and PCT were significantly affected by age (P < .001 and P < .001, respectively), whereas the regional difference in CT were independent of age (P = .076). Analysis of covariance including age, sex, and MNV group showed that regional difference in CT were significantly affected by sex, nasal peripapillary CT, and MNV group (P = .023, P < .001, and P < .001, respectively). The estimated marginal mean of the regional difference in CT was significantly smaller in the ceAMD group (1.671 ± 0.103) than in the normal control (2.250 ± 0.095, P = .003) and PNV groups (2.0880 ± 0.086, P < .001). Conclusions: Regional differences in CT were consistent with aging. However, the difference varied with the presence of PNV or ceAMD. Measurement of regional differences in CT provides additional information for characterizing the choroid in patients with MNV.

Choroidal blood perfusion could predict the sensitivity of myopia formation in Guinea pigs

Light Inhibits Lens-Induced Myopia through an Intensity-Dependent Dopaminergic Mechanism.

PurposeThe aim of the study was to analyze the effects of uneventful phacoemulsification surgery on choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT).MethodsIn this prospective study, 38 eyes of 38 patients having phacoemulsification surgery were included. All patients underwent detailed ophthalmologic examination, including preoperative axial length (AXL) measurement with optical biometry and intraocular pressure (IOP) measurement preoperatively and 1 month postoperatively. The CT was measured perpendicularly at the fovea and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal using SD-OCT preoperatively and 1 month postoperatively. Changes in the CT after surgery and correlation of this change with age, AXL, preoperative IOP, and IOP change were evaluated.ResultsThere was a statistically significant increase in the CT at all regions evaluated. This increment was more prominent in the nasal and subfoveal regions. The IOP decreased significantly 1 month after surgery (16.14±4.94 mmHg vs 13.91±4.86 mmHg; P<0.001). The change in IOP was correlated with the CT changes at all regions, whereas age, AXL, and preoperative IOP had no significant correlations with the changes in CT.ConclusionPhacoemulsification surgery may cause significant increase in CT, which is correlated with surgery-induced IOP change in the short term. Long-term follow-up of eyes having phacoemulsification surgery may provide further insight into the effects of cataract surgery on the choroid.

The aim of the present study was to examine and understand changes in platelet functions prior to and after the treatment of primary immune thrombocytopenia (ITP) in children. An automatic hematology analyzer and whole blood flow cytometry were used to detect immature platelet fraction (IPF), IPC and membrane glycoproteins (CD62p, PAC-1 and CD42b) in ITP children (ITP group), children with complete response after ITP treatment (ITP-CR group) and children with elective surgery (normal control group). The results showed that, levels of platelet count (PLT) and plateletcrit in the ITP group were lower alhtough the levels of mean platelet volume, platelet distribution width and platelet-large cell ratio (P-LCR) were higher than those in the normal control and ITP-CR groups. PLT in the ITP-CR group was lower than that in the normal controls. Additionally, IPF% was higher in the normal control and ITP-CR groups, IPC was lower in the ITP group compared to the normal control and ITP-CR groups. Furthermore, prior to ADP activation, the expression levels of CD62p, PAC-1 and CD42b in the ITP group were lower in ITP group than those in the normal control and ITP-CR groups. The expression level of PAC-1 was lower in the ITP-CR and normal control groups. No differences were identified in CD62p and CD42b expression levels. Following ATP activation, CD62p, PAC-1 and CD42b expression in the ITP group was lower than that in the normal control and ITP-CR groups. PAC-1 expression was lower while CD62p expression was higher in the ITP-CR group compared to the normal control group. In conclusion, the activation of platelets in ITP children was low. Decreased platelet function, platelet parameters and platelet glycoproteins may be used as markers for monitoring the treatment efficacy in ITP children.

The incidence of myopia has rapidly increased in recent decades, making it a growing public health concern worldwide. Interventions to suppress the progression of myopia are needed; one suggested strategy is the prevention of choroidal thinning, which can improve choroidal blood perfusion (ChBP). Bunazosin hydrochloride (BH) is an alpha1-adrenergic blocker and commercialized glaucoma eye drop that increases in blood circulation in the eye. In this study, we evaluated the efficacy of BH in suppressing the progression of myopia in a lens-induced murine model. Lens-induced myopia was induced in 3-week-old C57BL/6 J mice with -30 diopter (D) lenses for three weeks. Refractive error, axial length, and choroidal thickness were evaluated at three and six weeks of age using an infrared photorefractor and a spectral domain optical coherence tomography (OCT) system. Moreover, ChBP and scleral thickness were evaluated using swept-source OCT and histological analysis. Compared with the controls, the administration of BH eye drops suppressed the myopic shift of refractive error (mean difference ± standard error in the eye with -30D lens, -13.65 ± 5.69D vs. 2.55 ± 4.30 D; P<0.001), axial elongation (0.226 ± 0.013 mm vs. 0.183 ± 0.023 mm; P<0.05), choroidal thinning (-2.01 ± 1.80µm vs. 1.88 ± 1.27µm; P<0.001), and scleral thinning (11.41 ± 3.91µm vs. 19.72 ± 4.01µm; P<0.01) with myopia progression and increased ChBP (52.0% ± 4.1% vs. 59.5% ± 6.3%; P<0.05). The suppressive effect of BH eye drops was dose-dependent and higher than that of other glaucoma eye drops and alpha1 blockers. These results demonstrate the potential of BH eye drops in the treatment of myopia and support further investigation of their efficacy in humans. Further studies are needed to determine the mechanism of action and long-term safety of this treatment.

BackgroundThe aim was to investigate the correlation of serum cortisol level with choroidal thickness.MethodsSixty‐six healthy volunteers had no visual complaints or history of ocular disease. Subfoveal choroidal thickness at the foveal centre was measured with spectral domain optical coherence tomography (SD‐OCT). Morning serum cortisol levels were obtained at 8:00 am immediately following the SD‐OCT measurement. Measurements of only the right eyes were included in the study. Age, gender, axial length and spherical equivalent were noted. Correlation of choroidal thickness with age, gender, axial length, spherical equivalent and serum cortisol level were investigated with linear and multiple regression analysis.ResultsSixty‐six eyes of 66 patients were evaluated. Mean age was 43.4 ± 3.6 years (range: 40 to 53 years), mean spherical equivalent was ‐0.15-D (range: ‐1.25 to +1.50-D), mean axial length was 23.2-mm (range; 22.0 to 23.7-mm), mean choroidal thickness was 317.9 ± 45.1 μm (range: 206 to 394 μm). Age and spherical equivalent were not significantly correlated with choroidal thickness. Axial length had a strong negative correlation with choroidal thickness (R2: 0.488, p = 0.000). There was no significant correlation between serum cortisol level and choroidal thickness (R2: 0.034, p = 0.139).ConclusionOur results did not reveal any correlation between serum cortisol level and choroidal thickness. We believe that more prospective studies are needed to determine the relationship of cortisol and other hormones with choroidal thickness.

Purpose: To compare the macular choroidal thickness, ganglion cell complex thickness, peripapillary choroidal thickness and retinal nerve fiber layer thickness among normal, primary open angle glaucoma (POAG) and normal tension glaucoma (NTG) patients using RTVue (Fourier-domain optical coherence tomography; Optovue, Fremont, CA, USA).Methods: A retrospective analysis of 32 normal controls, 32 POAG and 52 NTG patients was performed.Choroidal thickness, ganglion cell complex thickness and retinal nerve fiber layer thickness were compared among normal controls, POAG and NTG subjects.Additionally, the factors influencing choroidal thickness (age, axial length, spherical equivalent, central corneal thickness, mean deviation, nocturnal dip, blood pressure variability) were analyzed.Results: A total of 32 normal controls, 32 POAG and 52 NTG patients were enrolled in this study.Macular and peripapillary choroidal thicknesses were significantly thinner in the NTG patients.In NTG subjects, the significant influencing factors associated with macular and peripapillary choroidal thicknesses were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness.In POAG patients, significant influencing factors associated with macular and peripapillary choroidal thicknesses were age and axial length.Conclusions: Choroidal thickness was significantly thinner in NTG patients compared with normal controls and POAG patients.Factors influencing choroidal thickness in NTG patients were age, axial length, nocturnal dip (diastolic blood pressure), diastolic blood pressure variability and ganglion cell complex thickness.In POAG patients, significant factors influencing choroidal thickness were age and axial length.

To describe the pattern and magnitude of diurnal variation of choroidal thickness (CT), its relation to systemic and ocular factors, and to determine the intervisit reproducibility of diurnal patterns. A prospective study was conducted on 12 healthy volunteers who each underwent sequential ocular imaging on two separate days at five fixed, 2-hour time intervals. Spectral domain optical coherence tomography (OCT) with enhanced depth imaging and image tracking was performed using a standardized protocol. Choroidal and retinal thicknesses were independently assessed by two masked graders. CT diurnal variation was assessed using repeated-measures ANOVA. A significant diurnal variation in CT was observed, with mean maximum CT of 372.2 μm, minimum of 340.6 μm (P < 0.001), and mean diurnal amplitude of 33.7 μm. Retinal thickness (mean, 235.0 μm) did not exhibit significant diurnal variation (P = 0.621). The amplitude of CT variation was significantly greater for subjects with thicker morning baseline CT compared with those with thin choroids (43.1 vs. 10.5 μm, P < 0.001). There were significant correlations between amplitude of CT and age (P = 0.032), axial length (P < 0.001), and spherical equivalent (P < 0.001). The change in CT also correlated with change in systolic blood pressure (P = 0.031). Comparing CT on two different days, a similar diurnal pattern was observed, with no significant difference between corresponding measurements at the same time points (P = 0.180). There is significant diurnal variation of CT, with good intervisit reproducibility of diurnal patterns on two different days. The amplitude of variation varies with morning baseline CT, and is correlated with age, axial length, refractive error, and change in systolic blood pressure.

To evaluate choroidal thickness at five macular locations and assess the correlations between choroidal thickness at these locations with age, refractive error, and axial length. Eighty-four eyes from 42 healthy adult volunteers were included. Enhanced depth imaging by spectral-domain optical coherence tomography was performed, and choroidal thickness was measured at five macular locations: subfoveal and 3 mm nasal, temporal, superior, and inferior. Correlations of choroidal thickness at each location with age, refractive error, and axial length were analyzed. Mean choroidal thicknesses at the subfoveal, superior, inferior, temporal, and nasal locations were 293, 308, 264, 263, and 174 μm, respectively. A correlation was found between choroidal thickness, age, refractive error, and axial length at all locations. Mean subfoveal choroidal thickness in healthy adults is approximately 300 μm. A correlation was found between choroidal thickness and all parameters studied.

PurposeTo compare the choroidal thickness (CT) of participants with various stages of age-related macular degeneration vs. normal controls through a meta-analysis of studies conducted within the Asian Eye Epidemiology Consortium.MethodsEight population-based studies from China, Iran, Japan, and Singapore were included. Axial length and spherical equivalent measurements and imaging with color fundus photography and spectral-domain optical coherence tomography were performed. Random-effects meta-analysis was performed to examine the association between AMD and its stages (early AMD, intermediate AMD [iAMD], neovascular AMD [nAMD], and geographic atrophy [GA]) with CT, while adjusting for age, sex, current smoking status, and axial length/spherical equivalent.ResultsOf 17,916 participants, 13,116 participants (mean age, 62.15 ± 9.66 years) were included into the study. The mean unadjusted CT was 245.01 ± 84.04 µm (mean CT, 255.4 µm [no AMD], 263.59 µm [early AMD], 270.64 µm [iAMD], 273.32 µm [nAMD], and 156.50 µm [GA]). The presence of AMD was associated with a thicker choroid (β = 11.51; 95% confidence interval [CI], 4.10–18.92). AMD severity was also positively associated with CT. Early AMD (β = 8.75; 95% CI, 0.03–17.47), iAMD (β = 19.68; 95% CI, 13.20–26.16), and nAMD (β = 34.15; 95% CI, 6.84–61.46) were each positively associated with a thicker CT after adjusting for age, sex, smoking, and spherical equivalent. GA was not significantly associated with CT.ConclusionsIn a large Asian cohort, AMD is associated with a thicker choroid in early AMD, iAMD, and nAMD, but not in GA. Studying the CT will help to better characterize Asian AMD phenotypes, which may show differences compared with AMD phenotypes in Western populations.

To explore the vascular risk factors and neuropsychological profiles of patients with magnetic resonance imaging (MRI)-defined subcortical ischemic depression (SID). Thirty-five SID patients, 37 patients with subcortical ischemic vascular disease without depression (SIVD) and 40 normal controls (NC) participated in this case-control study. The SID and SIVD groups were recruited from the Department of Neurology, First Affiliated Hospital, Anhui Medical University between October 2010 and September 2011. And the NC group came from Medical Center, First Affiliated Hospital of Anhui Medical University over the same period. The vascular risk factors of all participants were assessed by the Framingham scale. Depression symptoms were assessed by the geriatric depression scale (GDS) and Hamilton depression scale (HAMD) while cognitive functions by the mini-mental state examination (MMSE) and Montreal cognitive clock drawing task (CDT). Both the SID (12.3 ± 4.7) and SIVD (13.5 ± 3.4) groups showed significantly higher Framingham scores than the NC group (8.6 ± 1.8) (F = 20.850, P = 0.000). Compared with the NC group (28.3 ± 1.8; 23.1 ± 3.4; 8.0 ± 1.8), the MMSE, MoCA and CDT scores were significantly lower in the SID (26.7 ± 2.5; 20.0 ± 4.0; 2.0 ± 2.7) and SIVD (26.8 ± 1.9; 20.7 ± 3.0; 6.1 ± 2.1) groups (P < 0.05). There were significantly lower CAMCOG-C scores in the SID (82.7 ± 9.0) and SIVD (86.2 ± 6.9) groups versus the NC group (92.3 ± 6.2) (P < 0.05) and similarly in the SID group versus the SIVD group (P < 0.05). Among the subtests of CAMCOG-C, the orientation, language and memory scores in both SID (9.0 ± 1.4; 24.7 ± 4.0; 19.5 ± 3.4) and SIVD (9.4 ± 0.9; 25.5 ± 2.1; 20.3 ± 2.3) groups were significantly lower than those in the NC group (9.9 ± 0.4; 27.4 ± 1.9; 22.1 ± 2.4) (P < 0.05); the praxis scores in the SID group (9.4 ± 1.9) were significantly lower than those in the NC group (10.4 ± 1.5) (P < 0.05). And the thinking and perception scores in the SID group (5.4 ± 1.7; 6.3 ± 1.4) were significantly lower than those in the SIVD (6.2 ± 1.3; 7.0 ± 1.4) and NC (6.6 ± 1.3; 7.2 ± 1.4) groups. In the SID group, no significant correlation was found between the Framingham scores and neuropsychological assessments. There were a negative correlation between the GDS, HAMD scores and MMSE, MoCA, CAMCOG-C and CDT scores (P < 0.05). The SID patients demonstrate multiple neuropsychological deficits, especially in thinking, perception and praxis. No significant correlation between vascular risk factors and depression symptoms is found in SID patients.