CCDC66 mutations are associated with high myopia through affected cell mitosis.

BACKGROUND: High myopia (HM) refers to an eye refractive error exceeding -5.00 D, significantly elevating blindness risk. The underlying mechanism of HM remains elusive. Given the extensive genetic heterogeneity and vast genetic base opacity, it is imperative to identify more causative genes and explore their pathogenic roles in HM. METHODS: We employed exome sequencing to pinpoint the causal gene in an HM family. Sanger sequencing was used to confirm and analyse the gene mutations in this family and 200 sporadic HM cases. Single-cell RNA sequencing was conducted to evaluate the gene's expression patterns in developing human and mouse retinas. The CRISPR/Cas9 system facilitated the gene knockout cells, aiding in the exploration of the gene's function and its mutations. Immunofluorescent staining and immunoblot techniques were applied to monitor the functional shifts of the gene mutations at the cellular level. RESULTS: A suspected nonsense mutation (c.C172T, p.Q58X) in CCDC66 was found to be co-segregated with the HM phenotype in the family. Additionally, six other rare variants were identified among the 200 sporadic patients. CCDC66 was consistently expressed in the embryonic retinas of both humans and mice. Notably, in CCDC66-deficient HEK293 cells, there was a decline in cell proliferation, microtube polymerisation rate and ace-tubulin level. Furthermore, the mutated CCDC66 failed to synchronise with the tubulin system during Hela cell mitosis, unlike its wild type counterpart. CONCLUSIONS: Our research indicates that the CCDC66 variant c.C172T is associated with HM. A deficiency in CCDC66 might disrupt cell proliferation by influencing the mitotic process during retinal growth, leading to HM.

The efficacy of orthokeratology lenses with smaller back optic zone diameter in myopia control. A meta-analysis.

PURPOSE: This study was conducted to determine whether orthokeratology (OK) lenses with a smaller back optic zone diameter (BOZD) could exhibit stronger myopia control effects. METHOD: A meta-analysis was registered in PROSPERO (CRD42023408184). A comprehensive systematic database search was conducted, encompassing PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, Ovid, CNKI and CBM, to identify relevant studies up to 25 March 2023. The primary inclusion criteria for this meta-analysis were studies that investigated the myopia control effect of OK lenses with a small optical treatment area (≤5 mm). To assess the quality of the retrieved articles, two researchers evaluated them using the Cochrane bias risk assessment criteria. The primary outcome measures were the changes in axial length (AL) and refractive error, using the weighted mean differences (WMD) and 95% confidence intervals (CI) to assess differences between small and traditional back optical treatment zone groups in terms of these outcomes. RESULTS: The analysis encompassed five eligible studies, with a 1 year duration. The average difference in AL between the groups was 0.12 mm (WMD = -0.12, 95% CI [-0.16, -0.09], p < 0.00001). Likewise, the average difference in refractive error between the two groups was 0.44 D (WMD = 0.44, 95% CI [0.30, 0.57], p < 0.00001). None of the studies reported severe adverse events. CONCLUSIONS: Current evidence suggests that OK lenses with smaller back optical treatment zone are more effective in preventing myopia progression than traditional lenses. However, a longer-term evaluation is warranted.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

The Efficacy of Defocus Incorporated Multiple Segments Lenses in Slowing Myopia Progression: Results from Diverse Clinical Circumstances.

PURPOSE: Defocus incorporated multiple segments (DIMS) spectacle lenses were reported to slow myopia progression significantly in a randomized controlled trial (RCT). The study evaluated their effectiveness in clinical settings. DESIGN: Retrospective study. PARTICIPANTS: Patient records involving use of DIMS and single-vision (SV) spectacle lenses were collected from subsidiary hospitals of Aier Eye Hospital Group. METHODS: The spherical equivalent (SE), determined by subjective refraction, was adopted to assess the myopia progression. The strategy of propensity score matching (PSM) was applied to match the confounding baseline characteristics between the 2 groups. The effectiveness was calculated based on the difference of myopia progression of these 2 approaches. MAIN OUTCOME MEASURES: Change in SE. RESULTS: Three thousand six hundred thirty-nine patients with DIMS and 6838 patients with SV spectacles were included. The age of the patients was 6 to 16 years (mean ± standard deviation: 11.02 ± 2.53 years). The baseline SE was between 0.00 and -10.00 diopters (D) (mean ± standard deviation: -2.78 ± 1.74 D). After the PSM, data on 2240 pairs with 1-year follow-up and on 735 pairs with 2-year follow-up were obtained. Significantly slower progression was seen in the DIMS group at both the 1-year (DIMS, -0.50 ± 0.43 D; SV, -0.77 ± 0.58 D; P < 0.001) and 2-year (DIMS, -0.88 ± 0.62 D; SV, -1.23 ± 0.76 D; P < 0.001) subdataset. In the 1-year subdataset, 40% and 19% showed myopia progression of no more than 0.25 D for the DIMS and SV groups, respectively (chi-square, 223.43; P < 0.001), whereas 9% and 22% showed myopia progression of more than 1.00 D for the DIMS and SV groups, respectively (chi-square, 163.38; P < 0.001). In the 2-year subdataset, 33% and 20% showed myopia progression of no more than 0.50 D for the DIMS and SV groups, respectively (chi-square, 31.15; P < 0.001), whereas 12% and 29% showed myopia progression of more than 1.50 D for the DIMS and SV groups (chi-square, 65.60; P < 0.001). CONCLUSIONS: Although the magnitude was lower than that reported in the previous RCT, this large-scale study with diversity of the data sources confirmed the effectiveness of DIMS spectacles to slow myopia progression in clinical practice. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Outdoor Scene Classrooms to Arrest Myopia: Design and Baseline Characteristics.

PURPOSE: This study aimed to investigate the impact on childhood myopia of classrooms with spatial properties of classrooms resembling those of outdoor environments. This article describes the design, baseline characteristics, and the acceptability of this strategy. METHODS: Classrooms had custom-made wallpaper installed with forest and sky scenes that had spatial frequency spectra comparable with outdoor environments (i.e., outdoor scene classrooms). Acceptability of this strategy was evaluated by questionnaires. Outcomes to access the efficacy include cumulative proportion of myopia, change of cycloplegic spherical equivalent refractive error, and axial length. RESULTS: Ten classes, comprising 520 students, were randomly assigned into outdoor scene or tradition classrooms. There was no difference in refractive status between two groups (myopia/emmetropia/hyperopia, 16.3% vs. 49.4% vs. 34.2% in outdoor scene classrooms, 18.3% vs. 49.0% vs. 32.7% in traditional classrooms; P = .83). Compared with the traditional classrooms, 88.9% of teachers and 87.5% of students felt the outdoor scene classrooms enjoyable, 22.2% of teachers and 75.3% of students reported higher concentration, and 77.8% of teachers and 15.2% of students reported no change. In addition, 44.4% of teachers and 76.0% of students reported higher learning efficiency in the outdoor scene classrooms, and 55.6% of teachers and 18.3% of students reported no change. CONCLUSIONS: Outdoor scene classrooms are appealing to teachers and students. Outcomes of the study will inform the efficacy of this strategy in Chinese children.

Efficacy of contact lenses for myopia control: Insights from a randomised, contralateral study design.

PURPOSE: To determine the efficacy of two myopia control contact lenses (CL) compared with a single-vision (SV) CL. METHODS: Ninety-five Chinese children with myopia, aged 7-13 years in a 1-year prospective, randomised, contralateral, cross-over clinical trial with 3 groups; bilateral SVCL (Group I); randomised, contralateral wear of an extended depth of focus (EDOF) CL and SVCL (Group II) and MiSight® CL and SVCL (Group III). In Groups II and III, CL were crossed over at the 6-month point (Stage 1) and worn for a further 6 months (Stage 2). Group I wore SVCL during both stages. At baseline and the end of each stage, cycloplegic spherical equivalent refractive error (SE) and axial length (AL) were measured. Six-monthly ΔSE/ΔAL across groups was analysed using a linear mixed model (CL type, stage, eye and eye* stage included as factors). Intra-group paired differences between eyes were determined. RESULTS: In Group I, mean (SD) ΔSE/ΔAL with SVCL was -0.41 (0.28) D/0.13 (0.09) mm and -0.25 (0.27) D/0.16 (0.09) mm for stages 1 and 2, with a mean paired difference between eyes of 0.01 D/0.01 mm and 0.05 D/-0.01 mm, respectively. ΔSE/ΔAL with SVCL was similar across Groups I to III (Stage 1: p = 0.89/0.44, Stage 2: p = 0.70/ 0.64). In Groups II and III, ΔSE/ΔAL was lower with the EDOF and MiSight® CL than the contralateral SVCL in 68% to 94% of participants, and adjusted 6-month ΔSE/ΔAL with EDOF was similar to MiSight® (p = 0.49/0.56 for ΔSE/ΔAL, respectively). Discontinuations across the three groups were high, but not different between the groups (33.3%, 48.4% and 50% for Groups I to III, respectively [p = 0.19]) and most discontinuations occurred immediately after baseline. CONCLUSIONS: Extended depth of focus and MiSight® CL demonstrated similar efficacy in slowing myopia. When switched from a myopia control CL to SVCL, myopia progression was similar to that observed with age-matched wearers in SVCL and not suggestive of rebound.

Higher Circulating Levels of Neutrophils and Basophils Are Linked to Myopic Retinopathy.

This retrospective study investigated circulating immune cell alteration in patients with myopic retinopathy. Blood test results and demographic and ocular information of 392 myopic patients and 129 emmetropia controls who attended Changsha Aier Eye Hospital from May 2017 to April 2022 were used in this study. Compared with emmetropia, the percentages of neutrophils and basophils and neutrophil/lymphocyte ratio were significantly higher in myopic patients, whereas the percentages of monocytes and lymphocytes and the counts of lymphocytes and eosinophils were significantly lower in myopic patients. After adjusting for age and hypertension/diabetes, the difference remained. Interestingly, the platelet counts were significantly lower in myopic patients after the adjustments. Further subgroup analysis using multivariable linear regression showed that higher levels of neutrophils, neutrophil/lymphocyte ratio, and platelet/lymphocyte ratio, lower levels of monocytes, eosinophils, lymphocytes, and platelets, were related to myopic peripheral retinal degeneration (mPRD) and posterior staphyloma (PS). A higher level of basophils was linked to myopic choroidal neovascularization (mCNV). Our results suggest that higher levels of circulating neutrophils and neutrophil/lymphocyte ratio, lower monocytes, eosinophils, lymphocytes, and platelets are related to mild myopic retinopathy. A higher level of circulating basophils is related to the severe form of myopic retinopathy, such as mCNV.

RNA-Seq Analysis Reveals an Essential Role of the Tyrosine Metabolic Pathway and Inflammation in Myopia-Induced Retinal Degeneration in Guinea Pigs.

Myopia is the second leading cause of visual impairment globally. Myopia can induce sight-threatening retinal degeneration and the underlying mechanism remains poorly defined. We generated a model of myopia-induced early-stage retinal degeneration in guinea pigs and investigated the mechanism of action. Methods: The form-deprivation-induced myopia (FDM) was induced in the right eyes of 2~3-week-old guinea pigs using a translucent balloon for 15 weeks. The left eye remained untreated and served as a self-control. Another group of untreated age-matched animals was used as naïve controls. The refractive error and ocular biometrics were measured at 3, 7, 9, 12 and 15 weeks post-FDM induction. Visual function was evaluated by electroretinography. Retinal neurons and synaptic structures were examined by confocal microscopy of immunolabelled retinal sections. The total RNAs were extracted from the retinas and processed for RNA sequencing analysis. Results: The FDM eyes presented a progressive axial length elongation and refractive error development. After 15 weeks of intervention, the average refractive power was -3.40 ± 1.85 D in the FDM eyes, +2.94 ± 0.59 D and +2.69 ± 0.56 D in the self-control and naïve control eyes, respectively. The a-wave amplitude was significantly lower in FDM eyes and these eyes had a significantly lower number of rods, secretagogin+ bipolar cells, and GABAergic amacrine cells in selected retinal areas. RNA-seq analysis showed that 288 genes were upregulated and 119 genes were downregulated in FDM retinas compared to naïve control retinas. In addition, 152 genes were upregulated and 12 were downregulated in FDM retinas compared to self-control retinas. The KEGG enrichment analysis showed that tyrosine metabolism, ABC transporters and inflammatory pathways were upregulated, whereas tight junction, lipid and glycosaminoglycan biosynthesis were downregulated in FDM eyes. Conclusions: The long-term (15-week) FDM in the guinea pig models induced an early-stage retinal degeneration. The dysregulation of the tyrosine metabolism and inflammatory pathways may contribute to the pathogenesis of myopia-induced retinal degeneration.

Genipin inhibits the scleral expression of miR-29 and MMP2 and promotes COL1A1 expression in myopic eyes of guinea pigs.

PURPOSE: High myopia can lead to blindness. Genipin is a collagen cross-linking agent that may be used to treat myopia. However, the mechanism of action of genipin for the treatment of myopia is unclear. This study investigated the effect of genipin on the scleral expression of the miR-29 cluster, matrix metalloproteinase 2 (MMP2), and collagen alpha1 chain of type I (COL1A1) in a guinea pig model of myopia. METHODS: The model of myopia was established by treating guinea pigs with a - 8D lens on both eyes for 21 days, and eyes with a refractive error of - 6D or greater were included. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot were used to examine the mRNA and protein expression, respectively. A dual-luciferase assay was used to determine the direct targeting of the miR-29 cluster on the 3'-untranslated region (UTR) of the COL1A1 gene. RESULTS: The scleral expression of miR-29a, miR-29b, and miR-29c as well as MMP2 was significantly increased, and the scleral expression of COL1A1 was significantly decreased in the myopia group. Genipin treatment reversed these effects in myopic eyes. The dual-luciferase assay showed that the luciferase activities were significantly decreased in human embryonic kidney (HEK) cells transfected with miR-29a and miR-29b, but not miR-29c, compared with those transfected with control miRNAs. CONCLUSIONS: Genipin inhibits the scleral expression of the miR-29 cluster and MMP2 and promotes COL1A1 expression in a guinea pig model of myopia. Thus, genipin may promote COL1A1 expression by reducing the expression of the miR-29 cluster.

Temozolomide analog PMX 465 downregulates MGMT expression in HCT116 colorectal carcinoma cells.

The efficacy of temozolomide (TMZ) treatment for cancers is currently limited by inherent or the development of resistance, particularly, but not exclusively, due to the expression of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) in a significant proportion of tumors. We have found that TMZ analog C8-methyl imidazole tetrazine (PMX 465) displayed good anticancer activity against the colorectal carcinoma HCT116 cells which are MGMT-overexpressing and mismatch repair (MMR)-deficient. In this study, we found that PMX 465 could downregulate the expression of MGMT in HCT116 cells at the protein and mRNA levels. We found that PMX 465 could reduce MGMT expression by increasing the binding of wild-type p53 to the MGMT promoter and reducing the binding of Sp1 to the MGMT promoter.

Induction of dopamine D1 and D5 receptors in R28 cells by light exposures.

Dopamine is known to play an important role in the pathophysiological process of myopia development relevant to the ambient lighting, but it is still poorly understood about how lighting regulates dopamine and its interaction with dopamine receptors to mediate the pathogenic signal transduction leading to alterations of ocular globe and the pathogenesis of myopia. Many studies have highlighted changes of ocular dopamine amount in response to different lighting conditions, but little attention has been paid to the dopamine receptors during these processes. Here we examined the effects of different lighting exposures on the expression of dopamine receptors in rat R28 retinal precursor cells. R28 cells normally grown in dark were exposed to a low (10 lux) or high (500 lux) intensity of a source of LED white light (5000 K-6000 K) for 12 h and total RNA was isolated either immediately or after certain time continuous growing in dark. Both conventional and real-time RT-PCR were performed to determine the expression of all five different dopamine receptors in cells after treatments. While the transcripts of dopamine D2, D3, and D4 receptors were not detected in the total RNA preparations of all the cells, those of D1 and D5 receptors (DRD1 and DRD5) were induced by lighting in contrast to the dark control. Elevated levels of DRD1 and DRD5 mRNA returned back close to the original levels once the cells were maintained in dark after light exposures. Immunofluorescence microscopy using a specific antibody confirmed an increase in the immunoreactivity of DRD1 in the cells exposed to 500 lux lighting versus dark control. Notably, treatments of R28 cells with nanomolar dosages of dopamine (0-500 nM) directly downregulated expression of both DRD1 and DRD5, whereas haloperidol (0-50 nM), a DRD2 antagonist, significantly induced expression of DRD1. These results suggest that dopamine receptors in the retinal cells might actively respond to the environmental lighting to act as an important player in the activation of the dopaminergic system in the ocular structures relevant to the lighting-induced pathogenic development of myopia.

Changes in dopamine and ZENK during suppression of myopia in chicks by intense illuminance.

High ambient illuminances have been found to slow the development of deprivation myopia in several animal models. Almost complete inhibition of myopia was observed in chickens when intermittent episodes of high illuminance were alternated with standard office illuminance (50% duty cycle, alternate periods of 1 min 15,000 lux and 1 min 500 lux, continued for 10 h per day), or when illuminances were increased to 40,000 lux. Since the mechanisms by which bright light suppresses myopia are poorly understood, we have studied the roles of two well-established signaling molecules in myopia, dopamine and ZENK, in the chicken. In line with previous studies, we found that retinal dopamine release (as reflected by vitreal DOPAC content) was severely reduced during development of deprivation myopia. We found that illuminance of 15,000 lux, provided by quartz-halogen lamps, partially rescued the drop in retinal dopamine release. The finding is in line with the assumption that dopamine is involved in the light-induced inhibition of myopia. No differences in vitreal DOPAC were found when bright light was provided continuously or with 1:1 min alternating exposure with 500 lux. As previously described by others, wearing diffusers suppressed the expression of ZENK protein in glucagonergic amacrine cells (GACs) but neither continuous nor 1:1 min alternating bright to normal light could rescue the suppression of ZENK in GACs. While it is well known that light increases global retinal ZENK mRNA and protein levels, the changes of ZENK protein induced specifically in GACs by diffuser wear appear independent of light levels.

Identification of MFRP Mutations in Chinese Families with High Hyperopia.

PURPOSE: Mutations in MFRP have been reported to cause autosomal recessive posterior microphthalmia, nanophthalmos, and an ophthalmic syndrome characterized by posterior microphthalmia, high hyperopia, retinitis pigmentosa, foveoschisis, and optic disc drusen. High hyperopia is a consistent sign of this syndrome. The purpose of this study was to detect MFRP mutations in 46 unrelated Chinese probands with high hyperopia. METHODS: Clinical data and genomic DNA were collected from 46 Chinese probands diagnosed as having high hyperopia. Genomic DNA from 42 probands was initially analyzed by whole exome sequencing. MFRP variants were confirmed by Sanger sequencing. The coding sequence of MFRP for four additional probands was also analyzed by Sanger sequencing. Candidate MFRP variants were further validated in available family members and 192 normal individuals. RESULTS: Potential pathogenic compound heterozygous mutations, including c.287_291del (p.P96Lfs*6), c.1615C>T (p.R539C), c.664C>A (p.P222T), c.1150dup (p.H384Pfs*8), and c.1549C>T (p.R517W), were detected in three of the 46 probands included in this study. The clinical data revealed that all patients in this study had high hyperopia of +13.50D or higher and an eye axial length of 16.78 mm or less. Electroretinography showed normal responses in a patient with missense mutations and reduced rod responses in another patient with missense and truncation mutations in whom optical coherence tomography showed developmental cystoid macular degeneration in both eyes. CONCLUSIONS: The current study expands our knowledge of the mutation spectrum of MFRP and its associated phenotypes. To our knowledge, this is the first report of MFRP mutations in a Chinese cohort.

Burdens and trends of blindness and vision loss among those aged 55 years and older: A systematic analysis for the Global Burden of Disease Study 2019.

PURPOSE: To systematically analysis the burden and trends of blindness and vision loss for those aged ≥55 years from 1990 to 2019 and to predict trends over the next few years. METHODS: The data were extracted from the Global Burden of Disease Study (GBD) 2019. Trends from 1990 to 2019 were calculated using average annual percentage change (AAPC) by joinpoint regression analysis. Bayesian age-period-cohort (BAPC) models were used to predict future trends. RESULTS: In 2019, the global prevalence of blindness and vision loss was 471.1 million with 15.9 million disability-adjusted life-years (DALYs) for those aged ≥55 years. These numbers will reach 640.3 million cases and 18.9 million DALYs in 2030. The prevalence rate (per 100,000 population) increased from 32,137.8 (95% uncertainty interval [UI], 26,307.9-39,246.3) in 1990 to 33,509 (95% UI, 27,435.5-40,996.2) in 2019, with an AAPC of 0.143 (95% confidence interval [CI], 0.125-0.161; P < 0.001). The DALY rate (per 100,000 population) decreased from 632.9 (95% UI, 447.7-870.9) in 1990 to 579.3 (95% UI, 405.2-803.4) in 2019, with an AAPC of -0.293 (95% CI, -0.323-[-]0.263). Although the prevalence rates of cataracts, age-related macular degeneration, glaucoma, and near vision loss showed increasing trends from 1990 to 2019, the DALY rates indicated a downward trend for all blindness-causing diseases. The burden is heavier for women and in low Socio-demographic Index (SDI) regions. CONCLUSIONS: Despite a decline from 2001 to 2019, the burden of blindness and vision loss, measured by prevalence and DALYs, continues to rise after adjusting for population growth and aging. Blindness and vision loss are significant public health burdens, especially for women and in low-SDI regions.

Evaluation of PRSS56 in Chinese subjects with high hyperopia or primary angle-closure glaucoma.

PURPOSE: Mouse serine protease 56 (Prss56) mutants show a phenotype of angle-closure glaucoma with a shortened ocular axial length. Mutations in the human PRSS56 gene are associated with posterior microphthalmia and nanopthalmos. In this study, variations in PRSS56 were evaluated in patients with either primary angle-closure glaucoma (PACG) or high hyperopia. METHODS: A total of 561 participants were enrolled in this study, including 189 individuals with PACG, 110 individuals with simple high hyperopia (sphere refraction ≥+5.00 D), and 262 normal control subjects (-0.5 D

Treatment outcomes of myopic anisometropia with 1% atropine: a pilot study.

PURPOSE: To investigate the safety and efficacy of the treatment of myopic anisometropia with 1% atropine. METHODS: Twenty-two children with myopic anisometropia were prescribed 1% solution of atropine sulfate to the more myopic eye, one drop before sleep every 3 days. Children were visited every 3 to 4 months until the degree of anisometropia was no more than 0.5 diopters (D) ("Success") or unchanged after 9 months of treatment ("No effect"). The treatment effect was assessed by comparing the interocular imbalance in refraction and axial length before and after the treatment. A detailed questionnaire about subjective symptoms in each visit and an electroretinogram in the end were administered to evaluate the side effects of this treatment. RESULTS: The subjects were followed for 7 to 16 months. Six subjects withdrew participation on their own accord, and three were excluded because of inconstant usage of drug. Of the 13 remaining subjects, the refraction of the treated eyes decreased by 0.63 ± 0.59 D (p = 0.007), whereas that of the untreated eyes increased by -0.72 ± 0.65 D (p < 0.001). A corresponding trend was also found in the change of the axial length. Accordingly, the level of anisometropia was reduced from 1.82 ± 0.73 D to 0.47 ± 0.65 D (p < 0.001) and 10 (76.9%) of the 13 subjects were designated a "Success." One percent atropine was well tolerated by the children, and no electroretinogram abnormality was detected. CONCLUSIONS: The results from this pilot study indicate that monocular usage of a solution of 1% atropine sulfate is an effective treatment to reduce anisometropia, although with some tolerable side effects. Nevertheless, an attenuated benefit was observed after cessation of atropine treatment. Thus, participants should be informed of a possible rebound effect before the administration of atropine for myopic anisometropia.

GABAB Receptor Activation Affects Eye Growth in Chickens with Visually Induced Refractive Errors.

This study aims to explore the role of GABAB receptors in the development of deprivation myopia (DM), lens-induced myopia (LIM) and lens-induced hyperopia (LIH). Chicks were intravitreally injected with 25 µg baclofen (GABABR agonist) in one eye and saline into the fellow eye. Choroidal thickness (ChT) was measured via OCT before and 2, 4, 6, 8, 24 h after injection. ChT decreased strongly at 6 and 8 h after baclofen injection and returned back to baseline level after 24 h. Moreover, chicks were monocularly treated with translucent diffusers, -7D or +7D lenses and randomly assigned to baclofen or saline treatment. DM chicks were injected daily into both eyes, while LIM and LIH chicks were monocularly injected into the lens-wearing eyes, for 4 days. Refractive error, axial length and ChT were measured before and after treatment. Dopamine and its metabolites were analyzed via HPLC. Baclofen significantly reduced the myopic shift and eye growth in DM and LIM eyes. However, it did not change ChT compared to respective saline-injected eyes. On the other hand, baclofen inhibited the hyperopic shift and choroidal thickening in LIH eyes. All the baclofen-injected eyes showed significantly lower vitreal DOPAC content. Since GABA is an inhibitory ubiquitous neurotransmitter, interfering with its signaling affects spatial retinal processing and therefore refractive error development with both diffusers and lenses.

Applied Forces Changed Myopia Lens Optical Performance but Not Retinal Image Quality Tested Using a Newly Designed Digital Colmascope.

Background: The aim of this study was to investigate the effects of applied forces generated by a rim screw on the optical performance of mounted myopia lenses. The residual refractive error and retinal image quality of the corrected eyes were also investigated. Methods: For 120 lenses, internal lens stress was measured using a newly designed digital strain viewer (colmascope). Sixty myopic adults (120 eyes) were recruited. The effects of internal lens stress on residual refraction and retinal image quality were evaluated using OPD Scan III. The results were compared between loose and tight mounting and between the right and left eyes. Results: Significant differences were observed among nine lens zones in both the right and left lenses, regardless of the mounting state (P < 0.001). The differences were mainly derived from the five vertically arranged zones (P < 0.05). Significant differences in internal lens stress were observed between the right and left lenses (P < 0.05). No significant differences in central residual refractive error and retinal image quality of the corrected eyes were found between the loose- and tight-mounted lenses. Conclusion: The applied forces generated by the rim screw changed the peripheral optical performance of the mounted myopia lenses but exerted only negligible impacts on the central residual refractive error and visual image quality.

Two-Dimensional Peripheral Refraction and Image Quality for Four Types of Refractive Surgeries.

PURPOSE: To provide a comprehensive investigation of the optical quality across the visual field for current mainstream types of refractive surgeries. METHODS: Sixty eyes from 60 adults who received refractive surgery of either femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK), Q-value guided customized laser in situ keratomileusis (Q-LASIK), small incision lenticule extraction (SMILE), or Implantable Collamer Lens (ICL) (STAAR Surgical) implantation were included in this study. Refraction and optical aberrations from a visual field of horizontal 60° (from temporal 30° to nasal 30°) and vertical 36° (from superior 20° to inferior 16°) were measured using a custom-made Hartmann-Shack wavefront peripheral sensor. Refractive error, higher order aberrations, point spread function (PSF), and Strehl ratio were compared among these groups prior to and after the surgical procedures, respectively. RESULTS: All types of surgical procedures achieved an almost plano refraction in the central retina. This was also the case in the peripheral retina for the three types of laser refractive surgeries. However, residual peripheral relative hyperopic defocus was observed after ICL implantation. In all groups prior to the surgery, PSFs showed increasing distortion with eccentricity and arrow-like shape pointing toward the central fovea in the periphery in diagonals. Degradation of the PSFs was diminished by all three types of laser refractive surgeries, whereas ICL implantation made the peripheral distortion more prominent. CONCLUSIONS: Although ICL implantation produced a similar impact on refractive correction and objective optical quality in the central vision compared with other laser refractive surgeries, its outcome on the peripheral optics is different. The impact of this difference on visual performance deserves notice and warrants further investigation. [J Refract Surg. 2023;39(1):40-47.].

Two-step hierarchical neural network for classification of dry age-related macular degeneration using optical coherence tomography images.

Purpose: The aim of this study is to apply deep learning techniques for the development and validation of a system that categorizes various phases of dry age-related macular degeneration (AMD), including nascent geographic atrophy (nGA), through the analysis of optical coherence tomography (OCT) images. Methods: A total of 3,401 OCT macular images obtained from 338 patients admitted to Shenyang Aier Eye Hospital in 2019-2021 were collected for the development of the classification model. We adopted a convolutional neural network (CNN) model and introduced hierarchical structure along with image enhancement techniques to train a two-step CNN model to detect and classify normal and three phases of dry AMD: atrophy-associated drusen regression, nGA, and geographic atrophy (GA). Five-fold cross-validation was used to evaluate the performance of the multi-label classification model. Results: Experimental results obtained from five-fold cross-validation with different dry AMD classification models show that the proposed two-step hierarchical model with image enhancement achieves the best classification performance, with a f1-score of 91.32% and a kappa coefficients of 96.09% compared to the state-of-the-art models. The results obtained from the ablation study demonstrate that the proposed method not only improves accuracy across all categories in comparison to a traditional flat CNN model, but also substantially enhances the classification performance of nGA, with an improvement from 66.79 to 81.65%. Conclusion: This study introduces a novel two-step hierarchical deep learning approach in categorizing dry AMD progression phases, and demonstrates its efficacy. The high classification performance suggests its potential for guiding individualized treatment plans for patients with macular degeneration.