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.

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

Do monocular myopia children need to wear glasses? Effects of monocular myopia on visual function and binocular balance.

Objective: This study aims to compare the binocular visual functions and balance among monocular myopic adolescents and adults and binocular low myopic adolescents and explore whether monocular myopia requires glasses. Methods: A total of 106 patients participated in this study. All patients were divided into three groups: the monocular myopia children group (Group 1 = 41 patients), the monocular myopia adult group (Group 2 = 26 patients) and the binocular low myopia children group (Group 3 = 39 patients). The refractive parameters, accommodation, stereopsis, and binocular balance were compared. Results: The binocular refractive difference in Group 1, Group 2, and Group 3 was -1.37 ± 0.93, -1.94 ± 0.91, and -0.32 ± 0.27 D, respectively. Moreover, uncorrected visual acuity (UCVA), spherical equivalent (SE) and monocular accommodative amplitude (AA) between myopic and emmetropic eyes in Group 1 and Group 2 were significantly different (all P < 0.05). There was a significant difference in the accommodative facility (AF) between myopic and emmetropic eyes in Group 2 (t = 2.131, P = 0.043). Furthermore, significant differences were found in monocular AA (t = 6.879, P < 0.001), binocular AA (t = 5.043, P < 0.001) and binocular AF (t = -3.074, P = 0.003) between Group 1 and Group 2. The normal ratio of stereopsis according to the random dots test in Group 1 was higher than in Group 2 (χ2 = 14.596, P < 0.001). The normal ratio of dynamic stereopsis in Group 1 was lower than in Group 3 (χ2 = 13.281, P < 0.001). The normal signal-to-noise ratio of the binocular balance point in Group 1 was lower than Group 3 (χ2 = 4.755, P = 0.029). Conclusion: First, monocular myopia could lead to accommodative dysfunction and unbalanced input of binocular visual signals, resulting in myopia progression. Second, monocular myopia may also be accompanied by stereopsis dysfunction, and long-term uncorrected monocular myopia may worsen stereopsis acuity in adulthood. In addition, patients with monocular myopia could exhibit stereopsis dysfunction at an early stage. Therefore, children with monocular myopia must wear glasses to restore binocular balance and visual functions, thereby delaying myopia progression.

Changes of the effective optical zone after small-incision lenticule extraction and a correlation analysis.

The objective of the study is to observe the changes in the effective optical zone (EOZ) after small incision lenticule extraction (SMILE) and explore possible correlations with some influencing factors. In total, 133 eyes after SMILE were divided into the mild to moderate myopia group (- 1.75 D to - 5.75 D, 70 eyes) and the high myopia group (- 6.00 D to - 9.50 D, 63 eyes). The postoperative EOZ was calculated by utilizing the corneal tangential curvature map. Changes in EOZ (△-OZ) were monitored and compared between the two groups. Pearson correlation analysis was conducted to determine the correlation between △-OZ and corneal high-order wavefront aberrations. Multicollinearity analysis and ridge regression analysis were performed to assess the correlation between △-OZ and some corneal parameters. After SMILE, the horizontal EOZ (H-EOZ), vertical EOZ (V-EOZ), and average EOZ (A-EOZ) were significantly smaller than the programmed optical zone (POZ) in both groups (p < 0.05). The difference between V-EOZ and POZ (△V-OZ) and the difference between A-EOZ and POZ (△A-OZ) showed more significant changes in the high myopia group than in the mild to moderate myopia group, and △V-OZ was significantly larger than the difference between H-EOZ and POZ (△H-OZ) in the high myopia group. In both groups, the total high-order aberration (T-HOA) and spherical aberration (SA) both increased after SMILE, and they had a similar significant negative correlation with A-EOZ. Moreover, there was a significant negative correlation between △-OZ and Km (X1), Q-value (X2), spherical equivalent (SE, X3), ablating depth (AD, X4) and △e (X6), and a significant positive correlation between △-OZ and △Q (X5). △H-OZ was expressed as Y1, △V-OZ as Y2, and △A-OZ as Y3. The multiple linear regression equations were as follows: Y1 = 3.683 - 0.065X1, Y2 = 1.549 - 0.469X2 - 0.059X3, Y3 = 4.015 - 0.07X1 - 0.03X3, Y1 = 1.337 - 0.005X4 + 0.413X5, Y2 = 1.265 + 0.469X5, and Y3 = 0.852 - 0.002X4 - 0.398X6. The correlation degree with △A-OZ was ranked as Km > △Q > Q-value > AD > e-value > △e > SE > △Km, as represented by the ridge regression analysis. The EOZ was irregularly reduced after SMILE, which should be taken into consideration in the design of POZ, especially for high myopia. Consideration of the refractive diopter and corneal topography is advised for the design of POZ, the latter of which has greater reference significance.

Comparison of Efficacy and Safety Between Standard, Accelerated Epithelium-Off and Transepithelial Corneal Collagen Crosslinking in Pediatric Keratoconus: A Meta-Analysis.

Purpose: The purpose of the study is to compare the efficacy of standard epithelium-off CXL (SCXL), accelerated epithelium-off CXL (ACXL), and transepithelial crosslinking CXL (TECXL) for pediatric keratoconus. Methods: A literature search on the efficacy of SCXL, ACXL, and TECXL [including accelerated TECXL (A-TECXL)] for keratoconus patients younger than 18 years was conducted using PubMed, Cochrane Library, ClinicalTrials.gov, and EMBASE up to 2021. Primary outcomes were changes in uncorrected visual acuity (UCVA) and maximum keratometry (Kmax) after CXL. Secondary outcomes were changes in best-corrected visual acuity (BCVA), mean refractive spherical equivalent (MRSE), and central corneal thickness (CCT). Estimations were analyzed by weighted mean difference (WMD) and 95% confidence interval (CI). Results: A number of eleven identified studies enrolled 888 eyes (SCXL: 407 eyes; ACXL: 297 eyes; TECXL: 28 eyes; A-TECXL: 156 eyes). For pediatric keratoconus, except for a significant greater improvement in BCVA at 24-month follow-up in SCXL (WMD = -0.08, 95%CI: -0.14 to -0.01, p = 0.03, I2 = 71%), no significant difference was observed in other outcomes between the SCXL and ACXL groups. SCXL seems to provide greater changes in UCVA (WMD = -0.24, 95% CI: -0.34 to -0.13, p < 0.00001, I2 = 89%), BCVA (WMD = -0.09, 95% CI: -0.15 to -0.04, p = 0.0008, I2 = 94%), and Kmax (WMD = -1.93, 95% CI: -3.02 to -0.85, p = 0.0005, I2 = 0%) than A-TECXL, with higher incidence of adverse events. Conclusion: For pediatric keratoconus, both SCXL and ACXL appear to be comparable in the efficacy of visual effects and keratometric outcomes; SCXL seems to provide greater changes in visual and pachymetric outcomes than A-TECXL.

Polymicrobial keratitis after accelerated corneal collagen cross-linking in keratoconus: Case reports and literature review.

PURPOSE: To report two cases of polymicrobial keratitis following corneal collagen cross-linking for keratoconus and to review the literature. METHODS: Retrospective case note and literature review. RESULTS: The first case involved a 27-year-old male who presented with amebic corneal ulcers 3 days after the collagen cross-linking procedure. Some gram-negative (gram-ve) cocci were found upon staining, and cysts were observed by confocal microscopy at 7 days after surgery. Acanthamoeba infection mixed with gram-ve organisms was diagnosed. In the second case, a 14-year male developed Staphylococcus aureus corneal infection with anterior chamber empyema 3 days after the collagen cross-linking procedure for keratoconus. Occasional gram-positive (gram + ve) cocci and gram-ve bacilli were observed under a microscope. The mixed keratitis in the two patients resolved after systemic and topical antibiotic therapy, but the infection ultimately resulted in corneal scarring. Follow-up keratoplasty was needed to improve vision acuity in both patients. CONCLUSION: Although ultraviolet irradiation and the reactive oxygen released by riboflavin during collagen cross-linking have bactericidal effects, a lack of a corneal epithelial barrier, bandage contact lens usage, perioperative hygiene, and an abnormal immune state are risk factors for infectious keratitis after collagen cross-linking. Perioperative management of collagen cross-linking is important to prevent infection.

Transneuronal Degeneration in the Visual Pathway of Rats following Acute Retinal Ischemia/Reperfusion.

The maintenance of visual function not only requires the normal structure and function of neurons but also depends on the effective signal propagation of synapses in visual pathways. Synapses emerge alterations of plasticity in the early stages of neuronal damage and affect signal transmission, which leads to transneuronal degeneration. In the present study, rat model of acute retinal ischemia/reperfusion (RI/R) was established to observe the morphological changes of neuronal soma and synapses in the inner plexiform layer (IPL), outer plexiform layer (OPL), and dorsal lateral geniculate nucleus (dLGN) after retinal injury. We found transneuronal degeneration in the visual pathways following RI/R concretely presented as edema and mitochondrial hyperplasia of neuronal soma in retina, demyelination, and heterotypic protein clusters of axons in LGN. Meanwhile, small immature synapses formed, and there are asynchronous changes between pre- and postsynaptic components in synapses. This evidence demonstrated that transneuronal degeneration exists in RI/R injury, which may be one of the key reasons for the progressive deterioration of visual function after the injury is removed.

Comparison of the optical quality after SMILE and FS-LASIK for high myopia by OQAS and iTrace analyzer: a one-year retrospective study.

BACKGROUND: To compare the correction effect and optical quality after small-incision lenticule extraction (SMILE) and femtosecond laser assisted laser in situ keratomileusis (FS-LASIK) for high myopia. METHODS: 51 high myopia eyes after SMILE and 49 high myopia eyes after FS-LASIK were enrolled and divided into two groups retrospectively. The OQAS and iTrace analyzer were used for optical quality inspection. Between the two groups the spherical equivalent (SE), astigmatism, uncorrected distant visual acuity (UDVA), strehl ratio (SR), modulation transfer function cutoff frequency (MTF cutoff), objective scatter index (OSI) and wavefront aberrations were analyzed and compared before surgery and at 1, 6 and 12 months after surgery. RESULTS: After the operation: (1) SE and astigmatism declined and UDVA increased significantly in both groups, and UDVA was better after SMILE than FS-LASIK. (2) SR and MTF cutoff reduced and OSI increased significantly after SMILE and FS-LASIK. SR and MTF cutoff were significantly higher after SMILE than FS-LASIK. OSI was significantly lower after SMILE than FS-LASIK. (3) The total wavefront aberration, total low-order wavefront aberration, defocus and astigmatism aberration as well as trefoil aberration reduced significantly in both groups. The total high-order wavefront aberration increased significantly after FS-LASIK. The spherical and coma aberration increased significantly in both groups. The total high-order wavefront aberration and coma aberration at 1 month were higher after FS-LASIK than SMILE. CONCLUSION: The optical quality descended after SMILE and FS-LASIK. SMILE was superior to FS-LASIK at the correction effect and optical quality for high myopia. The combination of OQAS and iTrace analyzer is a valuable complementary measurement in evaluating the optical quality after the refractive surgery. TRIAL REGISTRATION: This is a retrospective study. This research was approved by the ethics committee of Xiangya Hospital and the IRB approval number is 201612074.

Detection of Static and Dynamic Stereopsis after Femtosecond Laser Small Incision Lenticule Extraction for High Myopia.

PURPOSE: The purpose of this study is to test binocular visual function after femtosecond laser small incision lenticule extraction (SMILE) for high myopia. The traditional Titmus stereotest and dynamic stereotest based on the visual perception biological model were used for comparative analysis. METHODS: A total of 43 patients were enrolled in this prospective study. At Week 1, Month 1, and Month 3 after surgery, the Titmus stereotest and dynamic stereotest generated by MATLAB were conducted. Dynamic stereopsis consists of randomly flickering Gabor spots and is divided into two models of high energy and low energy according to flicker frequency. RESULTS: The preoperative manifest refraction spherical equivalent was -7.21 ± 0.70 D. The preoperative anisometropia was 0.52 ± 0.54D. The quartiles of static stereoacuity in preoperation and 3 follow-ups were as follows: 50.00 (25.00, 100.00) in preoperation, 63.00 (40.00, 63.00) at Week 1, 40.00 (32.00, 63.00) at Month 1, and 40.00 (25.00, 50.00) at Month 3. Static stereopsis improved at Month 1 and Month 3 compared with preoperation and Week 1 (P < 0.05). There were statistically significant differences in high energy dynamic stereopsis at Week 1 and Month 1 compared to preoperation (P < 0.05). In addition, significant differences in low energy dynamic stereopsis were detected between Month 1 and preoperation and also at Month 3 compared to Month 1 (P < 0.05). CONCLUSION: Most high myopia patients have a dynamic stereopsis deficiency before refractive correction. SMILE surgery can improve both static and dynamic stereopsis early in the postoperation period. However, in the long term, there is no significant difference or even a decrease in dynamic stereopsis.

A microscopic study of the corneal stromal lenticules extracted during femtosecond laser-assisted small incision lenticule extraction.

The aim of the present study was to investigate the histological and morphological characteristics of corneal stromal lenticules extracted during femtosecond laser-assisted small incision lenticule extraction (SMILE) surgery by light and electron microscopy. A total of 20 human corneal stromal lenticules extracted during SMILE surgery were sent for microscopic examination immediately after surgery. Of these, six were observed under a light microscope and 14 were observed under an electron microscope. The smoothness of the front and rear surface of the lenticules observed under an electron microscope was rated on a scale of 0 to 4 according to unified evaluation criteria and the scores were statistically compared. Under the light microscope, the edge of the cross section of the corneal stromal lenticules was deeply stained and certain burrs and broken collagen fibers were observed. The swollen corneal stromal fibers were distributed irregularly, with a few bubbles of different sizes. Under the electron microscope, the surface of the lenticules ablated using a femtosecond laser was not perfectly smooth and the front surface was smoother than the rear surface. The side edge of the lenticules ablated using a femtosecond laser was not as regular as the edge cut using microscissors. Necrosis and dissolution of collagen fibers were observed near the surface of the lenticules. In conclusion, the surface quality of corneal stromal lenticules ablated using a femtosecond laser was not optimal when observed under a microscope. Increased attention should be paid to the histology and morphology of the corneal surface following laser ablation.

Clinical outcomes after small-incision lenticule extraction versus femtosecond laser-assisted LASIK for high myopia: A meta-analysis.

AIM: To compare postoperative clinical outcomes of high myopia after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). METHODS: From March 2018 to July 2020, PubMed, MEDLINE, Embase, the Cochrane Library, and several Chinese databases were comprehensively searched. The studies meeting the criteria were selected and included; the data were extracted by 2 independent authors. The clinical outcome parameters were analyzed with RevMan 5.3. RESULTS: This meta-analysis included twelve studies involving 766 patients (1400 eyes: 748 receiving SMILE and 652 receiving FS-LASIK). Pooled results revealed no significant differences in the following outcomes: the logarithm of the mean angle of resolution (logMAR) of postoperative uncorrected distance visual acuity (weighted mean difference (WMD) = -0.01, 95% confidence interval (CI): -0.02 to 0.00, I2 = 0%, P = 0.07 at 1 mo; WMD = -0.00, 95% CI: -0.01 to 0.01, I2 = 0%, P = 0.83 at 3 mo; WMD = -0.00, 95% CI: -0.01 to 0.00, I2 = 32%, P = 0.33 in the long term), and the postoperative mean refractive spherical equivalent (WMD = -0.03, 95% CI: -0.09 to 0.03, I2 = 13%, P = 0.30). However, the SMILE group had significantly better postoperative corrected distance visual acuity (CDVA) than the FS-LASIK group (WMD = -0.04, 95% CI, -0.05 to -0.02, I2 = 0%, P<0.00001). In the long term, postoperative total higher-order aberration (WMD = -0.09, 95% CI: -0.10 to -0.07, I2 = 7%, P<0.00001) and postoperative spherical aberration (WMD = -0.15, 95% CI: -0.19 to -0.11, I2 = 29%, P<0.00001) were lower in the SMILE group than in the FS-LASIK group; a significant difference was also found in postoperative coma (WMD = -0.05, 95% CI: -0.06 to -0.03, I2 = 30%, P<0.00001). CONCLUSION: For patients with high myopia, both SMILE and FS-LASIK are safe, efficacious and predictable. However, the SMILE group demonstrated advantages over the FS-LASIK group in terms of postoperative CDVA, while SMILE induced less aberration than FS-LASIK. It remains to be seen whether SMILE can provide better visual quality than FS-LASIK; further comparative studies focused on high myopia are necessary.

Clinical results of orthokeratology therapy in adolescents with low to moderate myopia. / é’å°‘å¹´ä½Žä¸­åº¦è¿‘è§†æ‚£è€ å¤œæˆ´è§’è†œå¡‘å½¢é•œçš„ä¸´åºŠæ•ˆæžœ.

OBJECTIVES: To observe the clinical results of orthokeratology therapy in adolescents with low to moderate myopia after wearing the lens for 6 months. METHODS: The data of 69 adolescents with low to moderate myopia were retrospectively analyzed. According to the degree of spherical power before treatment, the adolescents were divided into a low myopia group (34 cases, with spherical diopter from -3.00 to -0.75 D) and a moderate myopia group (35 cases, with spherical diopter from -5.75 to -3.25 D). The changes of the uncorrected distance visual acuity (UDVA), intraocular pressure, count of endothelial cell, eye axis length, Strehl ratio (SR), modulation transfer function (MTF), Q value, and wavefront aberrations before the treatment and 6 months after the treatment were compared and analyzed between the 2 groups. RESULTS: Compared with before the treatment, the UDVA improved significantly in the 2 groups (both P<0.05); the intraocular pressure and the count of endothelial cell did not change obviously in the 2 groups (all P>0.05), the eye axial length in the 2 groups was increased significantly (both P<0.05), but there was no significant difference between the 2 groups (all P>0.05); the Q value in the 2 groups was increased significantly, and the change was more obvious for the moderate myopia group (all P<0.05); the SR and MTF were increased remarkably in the 2 groups (all P<0.05), and there were no significant difference in the changes of SR and MTF between the 2 groups (both P>0.05); a considerable decrement was found for the total aberration, the total low-order aberration, and defocus (all P<0.05), and the changes were more significant in the moderate myopia group (all P<0.05); the total high-order aberrations were increased in the low myopia group (P<0.05); the increment of the vertical astigmatism, spherical aberration, horizontal coma, vertical coma, and horizontal trefoil were noticeable (all P<0.05), and the changes of the spherical aberration, vertical coma, and horizontal trefoil were more obvious in the moderate myopia group (all P<0.05). CONCLUSIONS: Orthokeratology can effectively improve the visual results of the adolescents with low to moderate myopia, and the corrective effect is more obvious for the adolescents with moderate myopia than those with low myopia.