Brimonidine as a possible treatment for myopia.

BACKGROUND: Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development. METHODS: Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively. RESULTS: Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective. CONCLUSION: Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.

Comparative visual outcomes of the first versus second eye following small-incision lenticule extraction (SMILE).

BACKGROUND: This study aimed to compare the visual outcomes of the first operated eyes with those of the second operated eyes following small-incision lenticule extraction (SMILE). METHODS: A total of 202 patients (404 eyes) underwent SMILE using the tear film mark centration method for myopia and myopic astigmatism correction. Baseline characteristics, objective optical quality, decentered displacement, induced corneal aberrations, and modulation transfer function (MTF) values were assessed. Linear regression analyzed the relationship between decentration and visual quality parameters, including corneal aberrations and MTF values. RESULTS: No significant difference was observed in objective visual quality, efficacy, and safety indexes between the two groups (all P > 0.05). The average decentered displacement for the first and second surgical eyes was 0.278 ± 0.17 mm and 0.315 ± 0.15 mm, respectively (P = 0.002). The horizontal coma in the first surgical eyes were notably lower than in the second (P = 0.000). MTF values at spatial frequencies of 5, 10, 15, and 20 cycles/degree (c/d) were higher in the first surgical eyes compared to the second (all P < 0.05). Linear regression indicated that high-order aberrations (HOAs), root mean square (RMS) coma, spherical aberration, horizontal coma, vertical coma, and eccentric displacement were all linearly correlated. Furthermore, MTF values exhibited a linear relationship with eccentric displacement across these spatial frequencies. CONCLUSIONS: There was no discernible difference in visual acuity, efficacy, or safety between the two operated eyes. Nonetheless, the first operated eyes exhibited reduced decentered displacement and demonstrated superior outcomes in terms of horizontal coma and MTF values compared to the second operated eyes following SMILE. The variations in visual quality parameters were linearly correlated with decentered displacement.

Predictive models of aging of the human eye based on ocular anterior segment morphology.

Aging is a major risk factor for various eye diseases, such as cataract, glaucoma, and age-related macular degeneration. Age-related changes are observed in almost all structures of the human eye. Considerable individual variations exist within a group of similarly aged individuals, indicating the need for more informative biomarkers for assessing the aging of the eyes. The morphology of the ocular anterior segment has been reported to vary across age groups, focusing on only a few corneal parameters, such as keratometry and thickness of the cornea, which could not provide accurate estimation of age. Thus, the association between eye aging and the morphology of the anterior segment remains elusive. In this study, we aimed to develop a predictive model of age based on a large number of anterior segment morphology-related features, measured via the high-resolution ocular anterior segment analysis system (Pentacam). This approach allows for an integrated assessment of age-related changes in corneal morphology, and the identification of important morphological features associated with different eye aging patterns. Three machine learning methods (neural networks, Lasso regression and extreme gradient boosting) were employed to build predictive models using 276 anterior segment features of 63,753 participants from 10 ophthalmic centers in 10 different cities of China. The best performing age prediction model achieved a median absolute error of 2.80 years and a mean absolute error of 3.89 years in the validation set. An external cohort of 100 volunteers was used to test the performance of the prediction model. The developed neural network model achieved a median absolute error of 3.03 years and a mean absolute error of 3.40 years in the external cohort. In summary, our study revealed that the anterior segment morphology of the human eye may be an informative and non-invasive indicator of eye aging. This could prompt doctors to focus on age-related medical interventions on ocular health.

Protective effects of sunlight exposure against PRK-induced myopia in infant rhesus monkeys.

PURPOSE: Extensive clinical evidence suggests that time spent outdoors might reduce the risk of myopia. This study aimed to determine whether increasing sunlight exposure has a protective effect on hyperopic-defocus induced myopia in a non-human primate. METHODS: Twelve 2-month-old rhesus monkeys were treated monocularly with photorefractive keratectomy (PRK) (4.0 D) and divided randomly into two groups: artificial light (AL; n = 6) and natural light (NL; n = 6). Monkeys in the AL group were reared under artificial (indoor) lighting (08:00-20:00 h). Monkeys in the NL group were exposed to natural (outdoor) lighting for 4 h (09:00-11:00 and 15:00-17:00 h). Ocular refraction, corneal power and axial dimensions were measured before sunlight exposure and every 10 days after PRK. At day 180, retinal histology and apoptosis activity were evaluated by hematoxylin and eosin (H&E) staining and terminal deoxynucleotidyl transferase biotin (dUTP) nick end labelling (TUNEL) assay. RESULTS: Mean (±SD) PRK induced anisometropia was +3.11 (0.33) D. At the end of the experiment, both eyes of the NL monkeys exhibited significantly more hyperopia and shorter vitreous chamber depths (VCD), compared with AL monkeys (p < 0.05). The NL group exhibited a significantly slower rate of compensation to the induced anisometropia than the AL group (p < 0.05). The retinas of both groups exhibited normal histology and levels of apoptosis. CONCLUSIONS: Moderate sunlight exposure exerts protective effects against the myopic shift resulting from PRK-induced defocus in monkeys. These results are consistent with current clinical findings that increased outdoor exposure protects against myopia development. Sunlight exposure should serve as an independent positive factor in human myopia control.

Earliella scabrosa-associated postoperative Endophthalmitis after Phacoemulsification with intraocular lens implantation: a case report.

BACKGROUND: Postoperative endophthalmitis after cataract surgery is a severe eye infection that can lead to irreversible blindness in the affected eye. The characteristics, treatment and prognosis of this disease vary because of its association with different pathogens. Here, we report what is possibly the first case of endophthalmitis after cataract surgery to be associated with the rare pathogen Earliella scabrosa. CASE PRESENTATION: A 56-year-old man from Hainan Island (China) with a history of phacoemulsification and type II diabetes mellitus underwent intraocular lens (IOL) implantation. He later presented with progressive endophthalmitis in his right eye. IOL explantation with capsular bag removal and a 23G pars plana vitrectomy combined with a silicone oil tamponade was performed. The infection was cleared without recurrence, and the patient's visual acuity improved from light perception to 20/200 in the right eye. An in vitro culture determined that the causative pathogen was Earliella scabrosa, and this result was confirmed by an internal transcribed spacer (ITS) sequence analysis. CONCLUSION: Earliella scabrosa has never been reported as an infectious agent in human eyes, and its clinical significance remains unknown. Here, we report a rare case of Earliella scabrosa-associated endophthalmitis after cataract surgery. The fungal infection presented as an acute attack and was successfully treated with vitrectomy.

Comparison of femtosecond laser-assisted corneal intrastromal xenotransplantation and the allotransplantation in rhesus monkeys.

BACKGROUND: In our previous study, we showed that both allogeneic and autogeneic small-incision femtosecond laser-assisted corneal intrastromal transplantation are safe and effective surgeries. However, the results of small-incision femtosecond laser-assisted intrastromal xenotransplantation have not yet been explored. Additionally, we suggest that glycerol-dehydrated corneal lamellae might provide a possible alternative for this xenogenic implantation approach. METHODS: Corneal inlay lamellae were produced from rabbits and humans using femtosecond laser-assisted surgeries and were dehydrated in glycerol for 1 week at 4 °C. These xenogeneic glycerol-dehydrated grafts and fresh allogeneic monkey lamellae were then implanted into rhesus monkeys using small-incision femtosecond laser assistance. Postoperatively, clinical examinations, AS-OCT measurements and tear inflammatory mediator assays were performed. RESULTS: There were no significant changes in the transparency of the corneal lamellae after glycerol dehydration. Following implantation, no evidence of tissue rejection or severe inflammatory responses was observed in the monkeys, and the host corneas remained transparent throughout a 6-month observation period. The grafts were clearly visible via AS-OCT. Corneal thickness increased 1 week postoperatively but subsequently declined and remained unchanged 1 month after surgery. Significant changes were observed in all tear inflammatory mediators in the 'Rabbit to Monkey' group. The trends in changes of tear inflammatory mediators in the 'Human to Monkey' group were similar to those in the 'Rabbit to Monkey' group. At 1 month post-surgery, the levels of most tear inflammatory mediators had decreased, with the exception of IL-1ß, TGF-ß1 and IFN-γ in the allotransplantation group. CONCLUSION: Small-incision femtosecond laser-assisted intrastromal transplantation minimized invasiveness and improved surgical efficiency. In addition, the host cornea maintained a high level of biocompatibility. Glycerol-dehydrated corneal lamellae might be potentially useful as an alternative inlay xenogeneic material. In this study, we also describe a new treatment that can be used in keratoconus, corneal ectasia, presbyopia, hyperpresbyopia and other diseases.

Corneal biomechanical properties in healthy children measured by corneal visualization scheimpflug technology.

BACKGROUND: The aim of this study was to evaluate corneal biomechanical properties in a population of healthy children in China using corneal visualization Scheimpflug technology (CST). METHODS: All children underwent complete bi-ocular examinations. CST provided intraocular pressure (IOP) and corneal biomechanical parameters, including time, velocity, length and deformation amplitude at first applanation (A1T, A1V, A1L, A1DA), at second applanation (A2T, A2V, A2L, A2DA), highest concavity time (HCT), maximum deformation amplitude (MDA), peak distance (PD), and radius of curvature (RoC). Pearson correlation analysis was used to assess the impacts of demographic factors, central corneal thickness (CCT), spherical equivalent (SE), and IOP on corneal biomechanics. RESULTS: One hundred eight subjects (32 girls and 76 boys) with the mean age of 10.80 ± 4.13 years (range 4 to18 years) were included in the final analyses. The right and left eyes were highly symmetrical in SE (p = 0.082), IOP (p = 0.235), or CCT (p = 0.210). Mean A1T of the right eyes was 7.424 ± 0.340 ms; the left eyes 7.451 ± 0.365 ms. MDA was 0.993 ± 0.102 mm in the right eyes and 0.982 ± 0.100 mm in the left eyes. Mean HCT of the right eyes was 16.675 ± 0.502 ms; the left eyes 16.735 ± 0.555 ms. All CST parameters of both eye were remarkably symmetrical with the exception of A2L (p = 0.006), A1DA (p = 0.025). The majority of CST parameters of both eyes were significantly correlated with CCT and IOP (p < 0.05). However, age, SE, and sex exert little influence on the CST measurements. CONCLUSIONS: This study found interocular symmetry in corneal biomechanics in healthy children eyes. Several CST biomechanical parameters in children are modified by CCT and IOP.

Corneal Biomechanical Properties in High Myopia Measured by Dynamic Scheimpflug Imaging Technology.

SIGNIFICANCE: The cornea is a viscoelastic tissue with viscous and elastic properties. The information of corneal biomechanical changes in high myopia has implications for understanding the pathogenesis of high myopia and primary open angle glaucoma. However, the knowledge of corneal biomechanics in high myopia is limited. PURPOSE: To compare the corneal biomechanical properties in high-myopia subjects and emmetropia subjects. METHODS: Dynamic Scheimpflug imaging technology was used to measure intraocular pressure, central corneal thickness, and corneal biomechanical parameters, including time at the first applanation, velocity at the first applanation, length at the first applanation, deformation amplitude at the first applanation, time at the second applanation, A2V (velocity at the second applanation), length at the second applanation (A2L), deformation amplitude at the second applanation, time at the highest concavity, radius curvature at the highest concavity (HCR), maximal deformation amplitude (MDA), and peak distance. RESULTS: This study included 40 subjects with high myopia and 61 emmetropia subjects. The high-myopia demonstrated greater MDA compared with the emmetropia (1.07 ± 0.01 vs. 1.02 ± 0.01 mm; P < .001) after adjusting for age and intraocular pressure. Pooling analysis found that the high myopia exhibited a smaller HCR, greater MDA, faster A2V and shorter A2L, with a pooled mean difference of -0.21 mm (95% confidential interval [95% CI], -0.30 to -0.13; P < .001) for HCR, 0.05 mm (95% CI, 0.04 to 0.06; P < .001) for MDA, -0.03 m/s (95% CI, -0.06 to -0.002; P = .034) for A2V, and -0.05 mm (95% CI, -0.08 to -0.02; P = .001) for A2L. CONCLUSIONS: Eyes with high myopia showed a significantly smaller HCR, greater MDA, faster A2V, and shorter A2L than did those with emmetropia, which indicated that the cornea in an eye with high myopia becomes weaker and more deformable.

Central corneal sensitivity after small incision lenticule extraction versus femtosecond laser-assisted LASIK for myopia: a meta-analysis of comparative studies.

BACKGROUND: The aim of this study was to evaluate central corneal sensitivity after small incision lenticule extraction (SMILE) versus femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) for myopia. METHODS: Eligible studies were identified by systematically searching PubMed, the Cochrane Library, Embase and the Chinese Biomedicine Database. Central corneal sensitivity after SMILE versus FS-LASIK was assessed by the pooled weighted mean differences (WMDs) of the reduction from pre-operation levels to 1 week, 1, 3 and 6 months following the operation. The quality of the included literature was assessed by the Quality Index. Data were synthesized by Stata 12.0 SE for Windows. RESULTS: Five studies involving 245 patients (363 eyes; 189 eyes in the FS-LASIK group and 174 eyes in the SMILE group) were included in the meta-analysis. The pooled results showed that there were no significant differences in central corneal sensitivity between FS-LASIK and SMILE before surgery (WMD = 0 mm, 95 % CI: -0.23 to -0.23, p = 0.998). At 1 week, 1 and 3 months after surgery, the central corneal sensitivity after FS-LASIK was lower than with SMILE (WMD = -17.35 mm, 95 % CI: -26.54 to -8.16, p <0.001; WMD = -17.52 mm, 95 % CI: -25.10 to -9.94, p <0.001; WMD = -14.64 mm, 95 % CI: -20.08 to -9.21, p <0.001, respectively). However, central corneal sensitivity after FS-LASIK was similar with SMILE 6 months after surgery (WMD = -2.02 mm, 95 % CI: -4.23 to 0.19, p = 0.074). CONCLUSION: Central corneal sensitivity exhibited a small decrease and a faster recovery after the SMILE procedure compared to FS-LASIK during the first three postoperative months. Corneal sensitivity after SMILE and FS-LASIK was similar at 6 months after surgery. However, these results should be interpreted with caution due to the limited number of studies.

Comparison of different corneal residual bed thickness after small incision lenticule extraction (SMILE).

PURPOSE: To evaluate the corneal biological parameters stability between the different corneal residual bed thickness (RBT) after Small Incision Lenticule Extraction (SMILE). METHODS: In this prospective clinical trial, 127 eyes of 64 patients underwent SMILE. According to the corneal RBT, the patients were divided into the 250-270 µm, 270-290 µm and 290-310 µm groups. Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany) and Scheimpflug camera (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany) measurements were performed preoperatively, 1 day, 1week, 1month and 3 months after surgery. RESULTS: The keratometer values among the three groups were no significant differences in postoperative periods (each P > 0.05), except the corneal thickness values (each P < 0.05). In the 250-270 µm and 270-290 µm groups, the keratometer and corneal thickness values were decreased at postoperative 1 week and increased at 1 and 3 months. The 290-310 µm group significantly higher posterior maximum elevation (PME) than the 250-270 µm group at 1 and 3 months (P = 0.022, 0.022, respectively), and higher preoperative thinnest point (PTE) at 1 week and 1 month (P = 0.013, 0.035, respectively). The PME of the 290-310 µm group was higher than the 270-290 µm group at 3 months (P = 0.045), and higher PTE at 1 week and 3 months (P = 0.022, 0.02, respectively). In all three groups, the maximal deformation amplitude (DA) was significantly higher at 1 and 3 months compared to postoperative 1 day and 1 week, and the IOP was decreased at 1 month then recovered at 3 months (each P < 0.05).The DA of the 250-270 µm group was significantly higher than the 290-310 µm group at postoperative 1 week, 1 and 3 months (P = 0.001, 0.01, 0.02, respectively). The change of the posterior corneal elevation and biomechanical parameters values were no significant differences among the three groups in postoperative periods (each P > 0.05). CONCLUSIONS: The range of 250-310 µm RBT was safe and stable at the early postoperative of SMILE. The RBT may be positively correlated with the posterior corneal elevation.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

Meibomian gland stem/progenitor cells: The hunt for gland renewal.

Meibomian glands (MGs) secrete lipid (meibum) onto the ocular surface to form the outermost layer of the tear film. Proper meibum secretion is essential for stabilizing the tear film, reducing aqueous tear evaporation, and maintaining the homeostasis of the ocular surface. Atrophy of MG as occurs with aging, leads to reduction of meibum secretion, loss of ocular surface homeostasis and evaporative dry eye disease (EDED). Since MGs are holocrine glands, secretion of meibum requires continuous self-renewal of lipid-secreting acinar meibocytes by stem/progenitor cells, whose proliferative potential is dramatically reduced with age leading to MG atrophy and an age-related meibomian gland dysfunction (ARMGD). Understanding the cellular and molecular mechanisms regulating meibocyte stem/progenitor cell maintenance and renewal may provide novel approaches to regenerating MG and treating EDED. Towards that end, recent label retaining cell and lineage-tracing experiments as well as knock-out transgenic mouse studies have begun to identify the location and identities of meibocyte progenitor cells and potential growth and transcription factors that may regulate meibocyte renewal. In addition, recent reports have shown that ARMGD may be reversed by novel therapeutics in mice. Herein, we discuss our current understanding of meibocyte stem/progenitor cells and the hunt for gland renewal.

Ocular Posterior Segment Distribution and Pharmacokinetics of Brimonidine After Intravitreal Administration in Guinea Pigs.

Purpose: Brimonidine is a highly alpha-2 adrenergic agonist, which provides a potential myopia control effect. This study aimed to examine the pharmacokinetics and concentration of brimonidine in the posterior segment tissue of eyes in guinea pigs. Methods: A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was successfully used for brimonidine pharmacokinetics and tissue distribution research in guinea pigs following intravitreal administration (20 µg/eye). Results: Brimonidine concentrations in the retina and sclera were maintained at a high level (>60 ng/g) at 96 h postdosing. Brimonidine concentration peaked in the retina (377.86 ng/g) at 2.41 h and sclera (306.18 ng/g) at 6.98 h. The area under curve (AUC0-∞) was 27,179.99 ng h/g in the retina and 39,529.03 ng h/g in the sclera. The elimination half-life (T1/2e) was 62.43 h in the retina and 67.94 h in the sclera. Conclusions: The results indicated that brimonidine was rapidly absorbed and diffused to the retina and sclera. Meanwhile, it maintained higher posterior tissue concentrations, which can effectively activate the alpha-2 adrenergic receptor. This may provide pharmacokinetic evidence for the inhibition of myopia progression by brimonidine in animal experiments.

Epidemiological study of refractive errors in children and adolescents of Han and Li ethnics in the Ledong and Wanning areas of Hainan Province.

Background: To determine the prevalence of refractive error and ocular biometric data (corneal curvature, axial length, and central corneal thickness) in 6 to 15 years old children of Li and Han ethnicities of China. Methods: This study was a cross-sectional study. A cluster sampling method was used to select 2 nine-year consistent schools in the Ledong and Wanning areas of Hainan Province, with a total of 4,197 students, 3,969 valid data. Eyesight test, slit lamp, autorefraction after cycloplegia, and ocular biometric assessment were performed. The chi-square test and logistic regression analysis was taken as the comparative method. Results: Myopia, hyperopia, and astigmatism are defined as: myopia: SE ≤-0.50 D; hyperopia: 0.50 D

EE-Explorer: A Multimodal Artificial Intelligence System for Eye Emergency Triage and Primary Diagnosis.

PURPOSE: To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. DESIGN: A diagnostic, cross-sectional, validity and reliability study. METHODS: EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. RESULTS: A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. CONCLUSION: The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.

Flicker downregulates the content of crystallin proteins in form-deprived C57BL/6 mouse retina.

Image degradation by loss of higher spatial frequencies causes form-deprivation myopia (FDM) in humans and animals, and cyclical illumination (flicker) at certain frequencies may prevent FDM. The molecular mechanisms underlying FDM and its prevention by flicker are poorly known. To understand them better, we have identified proteins that differ in amount in form-deprived (FD) mouse retinas, under steady versus flickering light. Male C57BL/6 mice (age 27-29 days) were randomly divided into three groups: Experimental - monocularly form-deprived, and kept under either normal room light ("FD-Only") or 20 Hz flickering light ("FD-Flicker"), throughout the 12-hour light phase; and Control ("Open-Control") - kept under normal illumination, without form deprivation. After two weeks of treatment, retinal proteins were extracted and separated by two-dimensional gel electrophoresis (2D-GE); proteins that differ in content in FD-only versus FD-flicker retinas were identified by mass spectroscopy ("MS"), and their identities were verified by western blotting. The contents of three identified proteins differed statistically in FD-only compared to FD-flicker retinas. These proteins were identified by MS as α-A-crystallin, crystallin ß A2 and crystallin ß A1. Quantitative western blotting showed that the relative amount of α-A-crystallin in FD-only retinas was significantly higher than that in FD-Flicker and control retinas. In conclusion, form deprivation induced significant increases in the amounts of crystallins in mouse retinas. These increases were significantly reduced by exposure to 20 Hz flicker. Since form deprivation is known to induce myopia development, and flicker to prevent it, our data suggest that FD- and flicker-responsive changes in the content of crystallin proteins may be involved causally or protectively in myopia development.

Determination of anterior segment changes with Pentacam after phacoemulsification in eyes with primary angle-closure glaucoma.

BACKGROUND: To investigate changes of anterior segment morphology in primary angle-closure glaucoma after phacoemulsification using the Pentacam system. DESIGN: Prospective, interventional study, Zhongshan Hospital of Sun Yat-sen University. PARTICIPANTS: Eighty-five eyes from 60 patients with primary angle-closure glaucoma undergoing phacoemulsification. METHODS: Intraocular pressure was measured by Goldmann applanation tonometry. Anterior segment morphology was assessed using the Pentacam camera. MAIN OUTCOME MEASURES: The intraocular pressure, central anterior chamber depth, peripheral anterior chamber depth, anterior chamber volume, pupil diameter and anterior chamber angle preoperative and 3 months postoperative. RESULTS: A total 78 eyes of 55 patients with primary angle-closure glaucoma were included in the analysis. Thirty-two eyes (41.0%) had acute primary angle-closure glaucoma, and 46 eyes (59.0%) had chronic primary angle-closure glaucoma. In both groups, statistically significant decreases in intraocular pressure and increases in anterior chamber volume, central anterior chamber depth, peripheral anterior chamber depth and anterior chamber angle inferiorly, nasally, temporally and superiorly were observed at 3 months after phacoemulsification (all P < 0.001). CONCLUSIONS: Phacoemulsification induces significant changes in anterior segment morphology in primary angle-closure glaucoma accompanied by a significant fall in intraocular pressure in the short term.

Spontaneous acinar and ductal regrowth after meibomian gland atrophy induced by deletion of FGFR2 in a mouse model.

PURPOSE: We have demonstrated that deletion of fibroblast growth factor receptor 2 gene (Fgfr2) leads to Meibomian gland (MG) atrophy in an inducible conditional knockout mouse model, referred as Fgfr2CKO. Herein, we investigated whether MG spontaneously recovers after atrophy in this model. METHODS: Two months old Fgfr2CKO mice were injected peritoneally once or twice of doxycycline (Dox) at 80 µg/gm of body weight to induce MG atrophy of various severities via Fgfr2 deletion. Recovery of acinar and ductal tissues was monitored by meibography, lipid staining and immunofluorescence against keratin-6a in MG whole-mount. Biomarkers for acinar and ductal differentiation and proliferation were also examined by immunostaining. RESULTS: Single Dox injection in Fgfr2CKO mice caused severe acinar and moderate ductal atrophy. Severe ductal shortening or loss occurred after second Dox injection, presumably related to the reported slower cycling of the ductal epithelia. Spontaneous acinar regrowth after atrophy was observed over a period of 60 days in both injection regimens. However, less robust acinar recovery was associated with more disrupted ductal structures in twice injected Fgfr2CKO mice. CONCLUSIONS: Our current findings further substantiate the role of FGFR2 in MG homeostasis, and suggest that FGFR2-signaling may provide a potential strategy for regenerating acini from age-related MG dysfunction in humans. Our data demonstrated that spontaneous MG recovery depends on the extent of ductal atrophy, suggesting that ductal epithelia may provide the progenitor cells for acinar regeneration. Nonetheless, the role of ductal tissue as the source of acinar progenitors awaits further investigation.

Effects of curcumin nanoparticles on proliferation and VEGF expression of human retinal pigment epithelial cells.

AIM: To investigate the effects of curcumin (Cur) nanoparticles loaded with chitosan derivatives grafted by deoxycholic acid (Chit-DC) on human retinal pigment epithelial (hRPE) cell proliferation and vascular endothelial growth factor (VEGF) mRNA expression. METHODS: Cur nanoparticles were synthesized with Chit-DC as the carrier and Cur as the supported drug. Cell counting kit-8 (CCK-8) method was used to detect the effects of different concentrations of Cur/Chit-DC, Chit-DC, and Cur on the proliferation of hRPE cells for different times. The changes of Cur/Chit-DC and Cur on hRPE cell cycle were determined by flow cytometry. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the mRNA expression levels of VEGF in hRPE cells treated with Cur, Chit-DC and Cur/Chit-DC at 10 µg/mL for 24h. RESULTS: Different concentrations of Chit-DC nanoparticle treated hRPE cells had no significant difference in terms of optical density (OD) values compared with the control group at 24h and 48h. Moreover, there was no change in the cell morphology under a light microscope. After 24h treatment with Cur/Chit-DC and Cur, the percentage of G0-G1 phase cells increased and the percentage of S phase cells decreased in all concentration groups. Cur/Chit-DC and Cur in all concentration groups inhibited the proliferation of hRPE cells in a time and dose dependent manner, and reduced the expression level of VEGF mRNA. CONCLUSION: The Cur/Chit-DC nanoparticles can release Cur continuously and have sustained release function. Both Cur/Chit-DC nanoparticles and Cur could inhibit hRPE cells cultured in vitro, and could reduce the expression level of VEGF mRNA in hRPE cells.