The treatment and risk factors of retinopathy of prematurity in neonatal intensive care units.

BACKGROUND: Retinopathy of prematurity (ROP) is a vascular proliferative disorder of the developing retina and a significant cause of childhood blindness around the world. The incidence of ROP is affected by many factors, and the incidence rate varies from country to country. The purpose of this study is to report the incidence and risk factors of ROP in neonatal intensive care unit (NICU) of Guangzhou First People's Hospital in China. METHODS: A retrospective review was performed on 436 premature infants who were consecutive ROP screened in the NICU of Guangzhou First People's Hospital from March 2013 to October 2017. The single-factor analysis and the logistic multivariate regression analysis were used to detect risk factors of ROP. RESULTS: Total 436 premature infants were consecutive ROP screened, 138 (31.65%) were found ROP, and 61(13.99%) were treated. The single-factor analysis revealed that the incidence of ROP was associated with multiple births, gestational age, birth weight, mechanical ventilation, intravascular hemolysis, the number of operations and blood culture results. The logistic multivariate regression analysis revealed that gestational age; birth weight, mechanical ventilation, minimum SaO2 and daily weight gain were independent risk factors for ROP onset. Forty-nine patients underwent retinal laser photocoagulation with recurrence 20 patients. Twelve patients underwent anti-VEGF drug (Ranibizumab) via intraocular injection with 5 patients of recurrence. CONCLUSIONS: The incidence of ROP in NICU of Guangzhou China will match those in middle-income countries, but higher than high-income countries. Anti-VEGF drugs could be preferred as a good treatment method for zone 1 ROP and aggressive posterior ROP.

Cyclic intensive light exposure induces retinal lesions similar to age-related macular degeneration in APPswe/PS1 bigenic mice.

BACKGROUND: Intensive light exposure and beta-amyloid (Aß) aggregates have been known as a risk factor for macular degeneration and an important component in the pathologic drusen structure involved in this disorder, respectively. However, it is unknown whether Aß deposition mediates or exacerbates light exposure-induced pathogenesis of macular degeneration. Several studies including the one from us already showed accumulation of Aß deposits in the retina in Alzheimer's transgenic mice. Using histopathological analysis combined with electroretinographic functional assessment, we investigated the effects of cyclic intensive light exposure (CILE) on the architecture of retina and related function in the APPswe/PS1bigenic mouse. RESULTS: Histopathological analysis has found significant loss of outer nuclear layer/photoreceptor outer segment and outer plexiform layer along with abnormal hypo- and hyper-pigmentation in the retinal pigment epithelium (RPE), remarkable choroidal neovascularization (CNV), and exaggerated neuroinflammatory responses in the outer retina of APPswe/PS1 bigenic mice following cyclic intensive light exposure (CILE), whereas controls remained little change contrasted with age-matched non-transgenic littermates. CILE-induced degenerative changes in RPE are further confirmed by transmission electron microcopy and manifest as formation of basal laminar deposits, irregular thickening of Bruch's membrane (BrM), deposition of outer collagenous layer (OCL) in the subretinal space, and vacuolation in the RPE. Immunofluorescence microscopy reveals drusenoid Aß deposits in RPE as well as neovessels attached which are associated with disruption of RPE integrity and provoked neuroinflammatory response as indicated by markedly increased retinal infiltration of microglia. Moreover, both immunohistochemistry and Western blots detect an induction of vascular endothelial growth factor (VEGF) in RPE, which corroborates increased CNV in the outer retina in the bigenic mice challenged by CILE. CONCLUSIONS: Our findings demonstrate that degenerative changes in the outer retina in the APPswe/PS1 bigenic mouse induced by CILE are consistent with these in AMD. These results suggest that an Alzheimer's transgenic animal model with accumulation of Aß deposits might be an alternative animal model for AMD, if combined with other confounding factors such as intensive light exposure for AMD.

Factors for Visual Acuity Improvement After Anti-VEGF Treatment of Wet Age-Related Macular Degeneration in China: 12 Months Follow up.

Purpose: To evaluate the treatment solutions and effectiveness of intravitreal ranibizumab (RBZ) or conbercept in patients with wet age-related macular degeneration (wAMD) in a real-life setting in China. Methods: The medical records of 368 patients with wAMD who started RBZ or conbercept treatment between 1 May 2014 and 30 April 2018 were evaluated. All patients were defined on fundus angiography at baseline to determine the subtype of AMD (PCV or CNV). We report visual acuity (VA) and central retinal thickness (CRT) measurements at baseline and 12 months. Results: The average number of anti-VEGF injections was 2.1 ± 1.2. The BCVA improvement of these two groups was similar with a difference of 1.00 letter (95% CI: -1.4~3.4, p = 0.8505). At the end of the study, a BCVA increase of at least 5 letters was determined to be a satisfactory efficacy endpoint. Several factors were related to the possible improvement in the satisfactory efficacy endpoint, including female sex (OR 2.07, 95% CI 1.22~3.51), number of injections (OR 1.40, 95% CI 1.12~1.75) and VA change at the first month (OR 13.75, 95% CI 7.41~25.51). Additionally, some factors were related to the possible reduction in the satisfactory efficacy endpoint, including diabetes (OR 0.27, 95% CI 0.10~0.73) and disease history (OR 0.75, 95% CI 0.57~0.98). Conclusion: Our study demonstrates that anti-VEGF drugs can effectively improve BCVA and reduce CRT in AMD patients. Sex, number of injections, VA change at the first month, diabetes and disease history are the most important factors affecting visual acuity.

Effect of Age and Myopia on Retinal Microvasculature.

BACKGROUND AND OBJECTIVE: To investigate the effect of age and refractive error on changes in the retinal microvascular network. PATIENTS AND METHODS: Subjects were recruited from the Doheny Eye Institute. Refractive error and axial length were measured. High myopia was defined as refractive error greater than -6 diopters (D). Optical coherence tomography angiography (OCTA) imaging was performed and images were analyzed using fractal analysis. Primary outcomes were superficial capillary plexus (SCP) vessel density, deep capillary plexus (DCP) vessel density, and foveal avascular zone (FAZ) area. RESULTS: One hundred thirty-eight eyes of 69 subjects were included. Twenty-eight (41%) subjects were male and 41 (59%) subjects were female. Mean age was 42.81 years ± 19.91 years (range: 8 years to 87 years). Mean refractive error was -1.74 D ± 3.18 D (range: -15.78 D to 4.25 D), and mean axial length (AL) was 24.29 mm ± 1.35 mm (range: 21.73 mm to 28.32 mm). SCP and DCP vessel densities were negatively correlated to age (r = -0.22, P = .011; and r = -0.49, P < .001). Controlling for age, patients with high myopia and longer AL had decreased SCP density (P = .021 and P = .027, respectively), but no difference in DCP vessel density was observed (P = .065 and P = .058, respectively). FAZ area was not significantly correlated to age, gender, refraction, or AL. CONCLUSIONS: SCP and DCP vessel densities decreased with age. In addition, SCP density but not DCP vessel density was reduced in eyes with high myopia and longer AL. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:925-931.].

Amyloid beta deposition related retinal pigment epithelium cell impairment and subretinal microglia activation in aged APPswePS1 transgenic mice.

AIM: To identify the pathological role of amyloid beta (Aß) deposition in retinal degeneration, and explore Aß deposition on the retinal pigment epithelium cells (RPE) layer and the associated structural and functional changes in Alzheimer's disease transgenic mice. METHODS: RPE changes in the eyes of APPswe/PS1 transgenic and none transgenic (NTG) mice over 20 months old were examined. Histological changes were investigated via hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) examination, whereas the expression of amyloid precursor protein (APP), Aß, Zonula occludens-1 (ZO-1) and Ionized calcium binding adaptor molecule-1 (IBA-1) were investigated using immunohistochemistry and immunofluorescence techniques. All of the obtained results were quantitatively and statistically analyzed. RESULTS: In aged transgenic mice, an APP-positive immunoreaction and Aß deposition were detected on the RPE layer but were undetectable in NTG mice. The RPE demonstrated some vacuole changes, shortened basal infoldings and basal deposition in histopathological examination and TEM tests, wherein irregular shapes were indicated by ZO-1 disorganization through fluorescence. Furthermore, IBA-1 positive cells were observed to have accumulated and infiltrated into the RPE layer and localized beneath the RPE/Bruch's membrane (BrM) complex, which was accompanied by an increase in BrM thickness in aged transgenic mice in comparison to NTG mice. The IBA-1 positive cells were found to be co-stained with Aß deposition on the RPE flat mounts. CONCLUSION: The observed Aß deposition in the RPE layer may cause RPE dysfunction, which is associated with microglia cells infiltration into the retina of aged transgenic mice, suggesting that Aß deposition probably plays a significant role in RPE-related degenerative disease.

Effects of confined space and near vision stimulation on refractive status and vitreous chamber depth in adolescent rhesus monkeys.

This study aimed to investigate the effects of sustained near vision stimulation, on the refractive development and elongation of the vitreous chamber in adolescent rhesus monkeys. A total of 12 adolescent rhesus monkeys (1.5-2.0 years old) were randomly assigned to 3 groups. In groups A (n=4) and B (n=4), monkeys were reared in close-vision cages for 8 and 4 h d(-1), respectively; tiny granules were added on the cage floor to avoid visual deprivation and to encourage near gaze. In group C (n=4), monkeys were reared in open-vision cages, with non-granule food as a control. Vitreous chamber depth, refractive status, and corneal refractive power were assessed over 18 months. Paired t-test was used to compare the differences and a P-value<0.05 was considered to be statistically significant. In group A, vitreous chamber depth and optical axis elongated significantly, and refractive error shifted towards myopia during the observation period. In group B, vitreous chambers and optical axis elongated but the refractive power did not show significant changes. In group C, there was no significant elongation in vitreous chambers and optical axis, and the refractive power changed slightly towards hypermetropia. There were no significant changes in corneal refractive power in each group. Sustained near vision can promote vitreous chamber growth and induce myopic shifts in refractive power in adolescent monkeys. Our results demonstrate the potential for a primate model of near-work-related myopia.

Generation of retinal ganglion-like cells from reprogrammed mouse fibroblasts.

PURPOSE: Somatic cells can be reprogrammed into an embryonic stem cell-like pluripotent state by Oct-3/4, Sox2, c-Myc, and Klf4. Sox2 as an essential reprogramming factor also contributes to the development of the eye and the retina. This study was conducted to determine whether induced pluripotent stem (iPS) cells express retinal progenitor cell (RPC)-related genes and whether iPS cells can directly differentiate into retinal ganglion cells (RGCs). METHODS: Mouse iPS cells were induced by the ectopically expressed four factors in tail-tip fibroblasts (TTFs). The expression of RPC-related genes in iPS cells was analyzed by RT-PCR and immunofluorescence. iPS cells were induced to differentiate into RGCs by the addition of Dkk1 + Noggin (DN) + DAPT and overexpression of Math5. iPS-derived retinal ganglion (RG)-like cells were injected into the retina, and the eyes were analyzed by immunohistochemistry. RESULTS: iPS cells inherently express RPC-related genes such as Pax6, Rx, Otx2, Lhx2, and Nestin. Overexpression of Math5 and addition of DN can directly differentiate iPS into retinal ganglion-like cells. These iPS-derived RG-like cells display long synapses and gene expression patterns, including Math5, Brn3b, Islet-1, and Thy1.2. Furthermore, inhibiting Hes1 by DAPT increases the expression of RGC marker genes. In addition, iPS-derived RG-like cells were able to survive but were unable to be integrated into the normal retina after transplantation. CONCLUSIONS: The four factor iPS cell inherently expressed RPC-related genes, and the iPS cell could be further turned into RG-like cells by the regulation of transcription factor expression. These findings demonstrate that iPS cells are valuable for regeneration research into retinal degeneration diseases.