Validation of Diagnostic Codes to Identify Glaucoma in Taiwan's Claims Data: A Multi-Institutional Study.

Background: Healthcare databases play a crucial role in improving our understanding of glaucoma epidemiology, which is the leading cause of irreversible blindness globally. However, the accuracy of diagnostic codes used in these databases to detect glaucoma is still uncertain. Aim: To assess the accuracy of ICD-9-CM and ICD-10-CM codes in identifying patients with glaucoma, including two distinct subtypes, primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). Methods: We analyzed electronic medical records data from a 2% random sample of patients who newly underwent visual field examination in Taiwan's largest multi-institutional healthcare system from 2011 to 2020. The diagnosis of glaucoma was confirmed by two ophthalmologists, based on the glaucoma diagnostic criteria. The positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for ICD-9-CM codes 365.1X and 365.2X, and ICD-10-CM codes H4010X, H4011X, H4012X, H4020X, H4021X, H4022X, H4023X and H4024X for glaucoma were calculated. Results: We randomly selected 821 patients (mean age: 56.9 years old; female: 50.5%) from the original cohort of 41,050 newly receiving visual field examination in the study. Among 464 cases with an ICD-9-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 86.5, 96.5, 91.9, and 90.9%, respectively. Among 357 cases with an ICD-10-CM glaucoma code, the sensitivity, specificity, PPV and NPV for glaucoma were 87.0, 92.8, 92.2 and 87.9%, respectively. The accuracy of diagnostic codes to identify POAG and PACG remained consistent. Conclusion: The diagnostic codes were highly reliable for identifying cases of glaucoma in Taiwan's routine healthcare practice. These results provide confidence when using ICD-9-CM and ICD-10-CM codes to define glaucoma cases in healthcare database research in Taiwan.

Exploring the Location of Corneal Pigmented Arc and Myopia Control Efficacy in Orthokeratology-Treated Children Using Pentacam Measurements.

OBJECTIVES: To determine the location and intensity of the corneal pigmented arc in orthokeratology (ortho-k)-treated children and its relationship with annual axial length (AL) change using Pentacam. METHODS: This retrospective cohort study enrolled children aged 9 to 15 years who had been followed up for at least one year after ortho-k treatment for myopia control. A Pentacam was used to determine the location and intensity of pigmented arc after lens wear. Annual AL changes were further used as the outcome measurement to determine their relationships with the location and intensity of pigmented arc using generalized estimating equations (GEE). RESULTS: In total, 62 eyes from 33 patients (mean age 10.9 years) were included in our final analysis. The mean follow-up time was 30.6 months. The mean annual AL changes were 0.10 mm. Age statistically correlated with annual AL change (GEE, P= 0.033). In addition, the annual AL change was negatively associated with the relative vertical distance of the lowest density of pigmented arc point based on the visual center, pupil center, and corneal thinnest point after adjustment with age ( P =0.005, P =0.004, and P< 0.001, respectively). CONCLUSIONS: Pentacam could be a useful tool for evaluating the location and intensity of the corneal pigmented arc. In addition, there was a negative correlation between the vertical distance of the pigmented arc and annual AL change. These findings may provide important information regarding myopia control, next-generation ortho-k design, and prescription.

Longitudinal changes in optical coherence tomography angiography characteristics in normal-tension glaucoma with or without high myopia.

PURPOSE: To evaluate the structural, microvascular, and functional progression of normal tension glaucoma (NTG) with or without high myopia by examining longitudinal changes in optical coherence tomography angiography (OCTA) and visual field (VF) parameters. METHODS: We evaluated 61 NTG eyes and classified 25 of the eyes with axial lengths (ALs) of ≥26 mm as highly myopic. We assessed the rate of change in OCTA parameters, namely radial peripapillary capillary (RPC) vessel density (VD), parafovea VD, deep parafovea VD, retinal nerve fibre layer (RNFL) thickness, and ganglion cell complex thickness. We evaluated the correlation of the rate of change in OCTA parameters with VF loss and AL. RESULTS: Among the 61 NTG eyes, rates of loss of RPC VD, parafovea VD, deep parafovea VD, and RNFL thickness were significantly different from zero despite the nonsignificant rate of change in VF mean deviation (MD). Changes in these OCTA parameters did not differ significantly in highly myopic NTG eyes. The rate of change in VF MD was significantly correlated with the rate of change in parafovea VD in highly myopic and non-highly myopic NTG eyes. In highly myopic NTG eyes, AL was negatively correlated with the rates of loss of RNFL thickness, VF MD, and VF PSD. CONCLUSION: NTG eyes with a relatively stable VF exhibited loss of VD and RNFL thickness. VF progression in NTG was correlated with decreasing parafovea VD, indicating a structure-function correlation. Greater AL may indicate faster VF loss and RNFL thinning in highly myopic NTG eyes.

MicroRNA-152-3p and MicroRNA-196a-5p Are Downregulated When Müller Cells Are Promoted by Components of the Internal Limiting Membrane: Implications for Macular Hole Healing.

Müller cells play a critical role in the closure of macular holes, and their proliferation and migration are facilitated by the internal limiting membrane (ILM). Despite the importance of this process, the underlying molecular mechanism remains underexplored. This study investigated the effects of ILM components on the microRNA (miRNA) profile of Müller cells. Rat Müller cells (rMC-1) were cultured with a culture insert and varying concentrations of ILM component coatings, namely, collagen IV, laminin, and fibronectin, and cell migration was assessed by measuring cell-free areas in successive photographs following insert removal. MiRNAs were then extracted from these cells and analyzed. Mimics and inhibitors of miRNA candidates were transfected into Müller cells, and a cell migration assay and additional cell viability assays were performed. The results revealed that the ILM components promoted Müller cell migration (p < 0.01). Among the miRNA candidates, miR-194-3p was upregulated, whereas miR-125b-1-3p, miR-132-3p, miR-146b-5p, miR-152-3p, miR-196a-5p, miR-542-5p, miR-871-3p, miR-1839-5p, and miR-3573-3p were significantly downregulated (p < 0.05; fold change > 1.5). Moreover, miR-152-3p and miR-196a-5p reduced cell migration (p < 0.05) and proliferation (p < 0.001), and their suppressive effects were reversed by their respective inhibitors. In conclusion, miRNAs were regulated in ILM component-activated Müller cells, with miR-152-3p and miR-196a-5p regulating Müller cell migration and proliferation. These results serve as a basis for understanding the molecular healing process of macular holes and identifying potential new target genes in future research.

Treatment of Myopia with Atropine 0.125% Once Every Night Compared with Atropine 0.125% Every Other Night: A Pilot Study.

(1) Purpose: To investigate the efficacy of myopia treatment in children using atropine 0.125% once every two nights (QON) compared with atropine 0.125% once every night (HS). (2) Methods: This retrospective cohort study reviewed the medical records of two groups of children with myopia. Group 1 comprised children treated with atropine 0.125% QON, while group 2 included children treated with atropine 0.125% HS. The first 6 months of data of outcome measurements were subtracted as washout periods in those children undergoing both atropine QON and HS treatment. The independent t-test and Pearson's chi-square test were used to compare the baseline clinical characteristics between the two groups. A generalized estimating equations (GEE) model was used to determine the factors that influence treatment effects. (3) Results: The average baseline ages of group 1 (38 eyes from 19 patients) and group 2 (130 eyes from 65 patients) were 10.6 and 10.2 years, respectively. There were no significant differences in axial length (AL) or cycloplegic spherical equivalent (SEq) at baseline or changes of them after 16.9 months of follow-up. GEE showed that the frequency of atropine 0.125% use has no association with annual AL (QON vs. HS: 0.16 ± 0.10 vs. 0.18 ± 0.12) and SEq (QON vs. HS: -0.29 ± 0.44 vs. -0.34 ± 0.36) changes in all children with myopia. It also showed that older baseline age (B = -0.020, p < 0.001) was associated with lesser AL elongation. (4) Conclusion: The treatment effects of atropine 0.125% HS and QON were similar in this pilot study. The use of atropine 0.125% QON may be an alternative strategy for children who cannot tolerate the side effects of atropine 0.125% HS. This observation should be confirmed with further large-scale studies.

Longitudinal follow-up of pediatric Graves' disease in preschool children: Clinical characteristics and a case report.

RATIONALE: Pediatric Graves' disease at preschool age is a rare condition. Previous reports have indicated that adolescents with this disease are girls. Pediatric Graves' ophthalmopathy in young children is rare, and long-term follow-up reports are lacking. PATIENT CONCERNS: The patient had hyperthyroidism and bilateral proptosis for 2 years, but she was only 4 years old. DIAGNOSES: The blood test revealed hyperthyroidism and the ophthalmic examination revealed proptosis. The patient had Graves' disease and Graves' ophthalmopathy. INTERVENTIONS: Initially, she was followed up in the pediatric department. Bilateral proptosis developed, and she was brought to the ophthalmology department for assistance. Orbital computed tomography revealed borderline enlargement of the extraocular muscles bilaterally. Other initial clinical findings included bilateral upper and lower eyelid trichiasis and mild punctate epithelial erosions of the cornea. She received conservative medical treatment in the ophthalmology department. OUTCOMES: Remission of hyperthyroidism was achieved 2 years after medical control. No elevated intraocular pressure, strabismus, or optic neuropathy developed during follow-up. Significant cosmetic improvement and gradual resolution of punctate epithelial erosions were found over 10 years. Finally, the patient had only mild bilateral lower trichiasis. LESSONS: Longitudinal follow-up revealed that the ocular manifestations of proptosis and eyelid trichiasis may have good outcomes. Proptosis gradually improved as the patient grew up.

Early Glaucoma Detection by Using Style Transfer to Predict Retinal Nerve Fiber Layer Thickness Distribution on the Fundus Photograph.

Objective: We aimed to develop a deep learning (DL)-based algorithm for early glaucoma detection based on color fundus photographs that provides information on defects in the retinal nerve fiber layer (RNFL) and its thickness from the mapping and translating relations of spectral domain OCT (SD-OCT) thickness maps. Design: Developing and evaluating an artificial intelligence detection tool. Subjects: Pretraining paired data of color fundus photographs and SD-OCT images from 189 healthy participants and 371 patients with early glaucoma were used. Methods: The variational autoencoder (VAE) network training architecture was used for training, and the correlation between the fundus photographs and RNFL thickness distribution was determined through the deep neural network. The reference standard was defined as a vertical cup-to-disc ratio of ≥0.7, other typical changes in glaucomatous optic neuropathy, and RNFL defects. Convergence indicates that the VAE has learned a distribution that would enable us to produce corresponding synthetic OCT scans. Main Outcome Measures: Similarly to wide-field OCT scanning, the proposed model can extract the results of RNFL thickness analysis. The structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR) were used to assess signal strength and the similarity in the structure of the color fundus images converted to an RNFL thickness distribution model. The differences between the model-generated images and original images were quantified. Results: We developed and validated a novel DL-based algorithm to extract thickness information from the color space of fundus images similarly to that from OCT images and to use this information to regenerate RNFL thickness distribution images. The generated thickness map was sufficient for clinical glaucoma detection, and the generated images were similar to ground truth (PSNR: 19.31 decibels; SSIM: 0.44). The inference results were similar to the OCT-generated original images in terms of the ability to predict RNFL thickness distribution. Conclusions: The proposed technique may aid clinicians in early glaucoma detection, especially when only color fundus photographs are available.

Association of Intraocular Pressure and Optical Coherence Tomography Angiography Parameters in Early Glaucoma Treatment.

This prospective study aimed to explore the effect of medical intraocular pressure (IOP) reduction on structural and capillary vessel density (VD) change by optical coherence tomography (OCT) angiography in early glaucoma. Patients with newly diagnosed glaucoma and a follow-up of ≥6 months were enrolled. An ocular examination that included slit-lamp bio-microscopy, pneumatic tonometry, gonioscopy, standard automated perimetry, and OCT angiography was performed. Quantitative OCT angiography parameters were assessed using a linear mixed model that was adjusted for inter-eye correlation. The correlations between IOP changes and OCT angiography parameter changes were analyzed using Spearman's correlation test. In total, 52 eyes of 36 participants, including 33 glaucoma eyes of 17 participants and 19 healthy eyes of 19 participants served as the case and control groups, respectively. The IOP of the case group decreased from a baseline mean of 20.4 ± 0.8 mmHg to 15.7 ± 0.5 mmHg at 3 months (p < 0.001) and to 16.1 ± 0.5 mmHg at 6 months (p < 0.001). For the subgroup with an IOP reduction of >20%, the deep macula VD was negatively correlated with baseline IOP and significantly decreased at 3 months follow-up. Additionally, change in retinal nerve fiber layer (RNFL) was positively correlated with a change in IOP at 6 months. In conclusion, the deep-layer macula VD was correlated with baseline IOP and influenced by the reduction in IOP in the short term. The changes in VD revealed the vulnerability of the deep vascular complex. The OCTA parameters provide in vivo monitoring information during medical treatment for early glaucoma.

Zebrafish (Danio rerio) Is an Economical and Efficient Animal Model for Screening Potential Anti-cataract Compounds.

Purpose: To develop a zebrafish cataract model for screening potential anti-cataract compounds. Methods: Living zebrafish were anesthetized and exposed to ultraviolet-C (UV-C) irradiation at a dosage of 3250 mJ/cm2/d until they developed severe cataracts. These cataracts were graded based on photographs analyzed with ImageQuant TL version 7.0. Fish with severe cataracts were used to evaluate a range of compounds for cataract treatment, including the previously demonstrated hit compound lanosterol. For the initial evaluation, fish were divided into four groups: no treatment, balanced salt solution, ß-cyclodextrin (ß-CD), and lanosterol dissolved in ß-CD. The treatments were performed for 10 days, and the clarity of lenses was evaluated. To assess the persistence of treatment, fish were treated with ß-CD and lanosterol dissolved in ß-CD for seven consecutive days followed by monitoring for three days without treatment. Results: The average time for zebrafish to develop severe cataracts using the present UV-C irradiation protocol was 7.8 days (range 4-15 days). Both study designs required only another 10 days to determine the effect of hit compounds. The total experimental period could be completed within one month, and the entire experiment was economical. Conclusions: We could assay a large number of hit compounds at a reasonable cost and within a short time using this newly developed zebrafish cataract model. These assays may allow development of an efficient platform for screening potential anti-cataract compounds. Translational Relevance: The results may facilitate the development of ani-cataract medication for humans after further experiments and investigations.

Trabeculectomy With Antimetabolite Agents for Normal Tension Glaucoma: A Systematic Review and Meta-Analysis.

Background: Evidence regarding the impact on visual field (VF), intraocular pressure (IOP), and antiglaucoma medications from trabeculectomy with antimetabolites for normal tension glaucoma (NTG) is conflicting because of insufficient study sample sizes. The aim of this study is to systematically assess VF progression rate, IOP control and antiglaucoma medication use after trabeculectomy with antimetabolites for progressing NTG. Methods: We searched published articles on PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from database inception to March 21, 2022. We selected studies that reported VF data before and after trabeculectomy with antimetabolite agents for NTG. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Data were extracted by 2 independent reviewers, and a random-effects model was employed for the meta-analysis. Study outcomes were VF progression rates measured using the pooled mean deviation (MD) slope, changes in antiglaucoma medications, and IOP. Subgroup analyses of the MD slope according to mean age (over or under 65 years), baseline MD (over or under -12 dB), and baseline IOP (over or under 15 mmHg) were performed to determine the results' robustness. Results: We included 7 retrospective observational studies (Japan: 6 studies, United States: 1 study) comprising a total of 166 eyes. Mean preoperative VF MD slopes ranged from -0.52 to -1.05 dB/year. The meta-analysis demonstrated significant MD slope improvement after trabeculectomy (pooled mean difference: 0.54 dB/year, 95% CI: 0.40 to 0.67, I2 = 9%). Mean age, baseline MD, and baseline IOP subgroup analyses revealed MD slope results were consistent with those of the main analyses. The mean IOP (pooled mean difference: -5.54 mmHg, 95% CI: -6.02 to -5.06, I2 = 0%) and mean number of antiglaucoma medications (pooled mean difference: -1.75, 95% CI: -2.97 to -0.53, I2 = 98%) significantly decreased after trabeculectomy. The most frequently reported early complications after trabeculectomy were hypotony, hyphema, and shallow anterior chamber. Conclusion: This systematic review and meta-analysis indicated that trabeculectomy with antimetabolites is beneficial for progressing NTG; it preserves visual function by alleviating the MD slope and reducing antiglaucoma medication use. However, several post-trabeculectomy complications should be monitored.

Thinner Central Corneal Thickness is Associated with a Decreased Parapapillary Vessel Density in Normal Tension Glaucoma.

This retrospective cross-sectional study, which enrolled 124 normal tension glaucoma (NTG) eyes and 68 healthy eyes as the control, determined the association between central corneal thickness (CCT) and ocular parameters in NTG. CCT was measured using the Pentacam® system, optical coherence tomography angiography (OCT-A) was adopted to measure the peripapillary and macular area VDs, and spatial data were based on the Garway-Heath map as illustrated in OCT-A. Univariate and multivariate linear regressions were used to statistically analyze for associations between CCT and other factors. In this study, the mean age was similar for both the NTG and control groups. The mean CCT of the NTG group was significantly thinner than that of the control group (533.97 ± 33.11 µm vs. 546.78 ± 38.21 µm; p = .022). Considering all the factors, CCT negatively correlated with visual field (VF) pattern standard deviation (univariate, p = .045). To analyze structural and functional factors separately, we found a significant positive correlation between CCT and whole disc radial peripapillary capillary VD (VDRPC; multivariate, p = .019). To analyze the relationship between all factors and sectoral changes in VDRPC, a significant positive correlation was observed between CCT and inferior temporal VDRPC (univariate, p = .039) and inferior nasal VDRPC (VDRPC IN; univariate, p = .048). In conclusion, this novel study shows that among NTG participants, a thinner cornea correlated with weaker biomechanical properties susceptible to optic nerve tissue displacement, especially in response to mild transient elevation of IOP, leads to compromised ocular microcirculation.

Efficacy of Myopia Control and Distribution of Corneal Epithelial Thickness in Children Treated with Orthokeratology Assessed Using Optical Coherence Tomography.

The association between myopia control efficacy in children treated with orthokeratology and corneal epithelial thickness is still unknown. The aim of this study was to explore the corneal epithelial thickness and its association with axial length changes in children treated with orthokeratology. This retrospective cohort study enrolled children aged from 9 to 15 years who had received orthokeratology for myopia control and had been followed up for at least 1 year. Anterior segment optical coherence tomography was performed to generate wide epithelial thickness maps of the patients. Annual axial length changes were calculated from the axial length at 6 months after the initiation of orthokeratology lens wear and at final measurements. Corneal epithelial thickness data were obtained from 24 sectors and a central 2 mm zone of the wide epithelial thickness map. Associations between annual axial length changes and corneal epithelial thickness for each sector/zone of the wide epithelial thickness map, and orthokeratology treatment data were determined by generalized estimating equations. Finally, a total of 83 eyes of 43 patients (mean age 11.2 years) were included in the analysis. The mean annual axial length change was 0.169 mm; when regressing demographic and ortho-k parameters to mean annual axial length changes, age and target power were both negatively associated with them (ß = -14.43, p = 0.008; ß = -0.26, p = 0.008, respectively). After adjusting for age and target power, the annual axial length changes were positively associated with the corneal epithelium thickness of IT1, I1, SN2, and S2 sectors of the wide epithelial thickness map, and negatively with that of the I3 sector. In conclusion, we identified associations between annual axial length changes and the corneal epithelium thickness of certain sectors in children treated with orthokeratology. This may facilitate the design of orthokeratology lenses with enhanced efficacy for myopia control.

Prospective evaluation of the comorbidity of obstructive sleep apnea in patients with glaucoma.

STUDY OBJECTIVES: This study aimed to identify prospectively the correlation between obstructive sleep apnea (OSA) severity, ocular microcirculation changes, and visual function changes in patients with glaucoma. METHODS: We prospectively enrolled patients with glaucoma who were willing to undergo overnight polysomnography. The enrolled patients were further divided into normal tension glaucoma, high-tension glaucoma, and control. Visual field progression was analyzed using sequential standard automated perimetry. Peripapillary and macular vessel density were assessed through optical coherence tomography angiography (OCT-angiography). The associations between polysomnography parameters, OCT-angiography parameters, and visual field progression were analyzed. RESULTS: A total of 22 patients with normal tension glaucoma, 30 patients with high-tension glaucoma, and 24 control patients were enrolled. Through regression analysis, glaucoma was found to be an independent predictor of moderate-to-severe OSA (P = .035); furthermore, moderate-to-severe OSA was significantly associated with visual field progression (P = .008 in the high-tension glaucoma subgroup and P = .008 in the overall glaucoma). Additionally, OSA severity was negatively correlated with the ganglion cell complex thinning rate in the normal tension glaucoma subgroup. CONCLUSIONS: Presence of glaucoma increased the risk of moderate-to-severe OSA compared with the control group. OSA severity was related to visual field deterioration in patients with glaucoma and further associated with structural progression in the normal tension glaucoma subgroup. Careful monitoring of the comorbid OSA status of patients with glaucoma is essential to prevent disease progression. CITATION: Chan Y-H, Chuang L-H, Yu C-C, et al. Prospective evaluation of the comorbidity of obstructive sleep apnea in patients with glaucoma. J Clin Sleep Med. 2022;18(1):47-56.

Micropulse transscleral cyclophotocoagulation in a Taiwanese population: 2-year clinical outcomes and prognostic factors.

PURPOSE: To evaluate the 2-year efficacy and safety of micropulse transscleral cyclophotocoagulation (MP-TSCPC) in Taiwanese patients with glaucoma. METHODS: We included the patients who received standardized MP-TSCPC with follow-up examinations on a regular basis for 24 months. Treatment success was defined as the attainment of a postoperative intraocular pressure (IOP) between 6 and 21 mmHg or a ≥ 20% reduction in IOP from baseline without an increase in glaucoma medications. RESULTS: A total of 60 eyes from 56 patients who underwent MP-TSCPC for refractory glaucoma were included. The median age at MP-TSCPC intervention was 58.9 ± 12.4 years. The percentage of treatment success was 88.3% at 3 months, 83.3% at 6 months, 78.3% at 12 months, and 75.0% at 24 months. The mean baseline IOP prior to MP-TSCPC was 34 ± 11.9 mmHg (range 14-56 mmHg). The mean postoperative IOP decreased to 20.9 ± 10.0 mmHg, 18.0 ± 7.8 mmHg, 17.5 ± 6.4 mmHg, and 18.2 ± 7.1 mmHg after 3 months, 6 months, 12 months, and 24 months, respectively, in successful cases. The mean number of glaucoma medications at baseline was 3.8 ± 0.2, and the mean numbers of glaucoma medications at postoperative months 3, 6, 12, and 24 were 2.6 ± 0.7, 2.8 ± 0.6, 2.5 ± 1.4 and 2.6 ± 1.4, respectively, in successful cases. Younger age and prior CW-TSCPC significantly contributed to surgical failure in the multivariate model. Complications after MP-TSCPC included mild anterior chamber inflammation, conjunctival hemorrhage, hypotony, and mydriasis, and all subsided after treatment. None of the eyes developed vitreous hemorrhage, cystoid macular edema, or phthisis bulbi in the late postoperative period. CONCLUSIONS: This study demonstrated that younger age and prior CW-TSCPC were risk factors for MP-TSCPC failure within 2 years. MP-TSCPC might be safe and effective for refractory glaucoma patients with maximal antiglaucoma medications.

Evaluation of axial length to identify the effects of monocular 0.125% atropine treatment for pediatric anisometropia.

The aim of the study is to determine the effects of monocular 0.125% atropine daily treatment on the longer axial length (AL) eyes in children with pediatric anisometropia. This was a retrospective cohort study. The charts of children with anisometropia (aged 6-15 years) who had a > 0.2-mm difference in AL between the two eyes were reviewed. Children who received monocular treatment of 0.125% atropine in the eye with longer AL were included for final analysis. The main outcome measure was the difference in AL between the two eyes after treatment. Regression analysis was used to model the changes in AL according to the time of treatment in both eyes. Finally, forty eyes in 20 patients (mean age 10.2 years) were included in the analyses. During the treatment period, AL was controlled in the treated eyes (p = 0.389) but elongated significantly in the untreated eyes (p < 0.001). The difference in AL between the treated and untreated eyes decreased from 0.57 to 0.22 mm (p < 0.001) after the 1-year treatment period. In the regression model, the best fit for the relationship between changes in AL and time during the treatment period in the treated eyes was the quadratic regression model with a concave function. In conclusion, these data suggest that 0.125% atropine daily is an effective treatment to reduce the interocular difference of AL in eyes with axial anisometropia. This pilot study provides useful information for future prospective and larger studies of atropine for the treatment of pediatric axial anisometropia.

Foveal Microvascular Integrity Association With Anti-VEGF Treatment Response for Diabetic Macular Edema.

Purpose: To investigate the association between foveal microvascular integrity and anti-vascular endothelial growth factor (VEGF) treatment response for diabetic macular edema (DME). Methods: This retrospective study enrolled 58 eyes (from 45 patients) with DME. Treatment strategy was three to five monthly anti-VEGF injections followed by a PRN protocol. Treatment with an intravitreal corticosteroid would be considered for persistent DME after five consecutive anti-VEGF injections. Eyes achieving a treatment-free interval ≥ four months within two years were classified into the good clinical course group (group 1). Eyes with frequent recurrent edema (treatment-free interval < four months) or requiring an intravitreal corticosteroid within two years were classified into the suboptimal clinical course group (group 2). Foveal microvascular integrity was evaluated by two continuous variables, that is, vessel density (%) within a width of 300 µm around the foveal avascular zone (FD-300) on optical coherence tomography angiography (OCTA) and perifoveal leakage (area %) on fluorescein angiography (FA). Results: There were 37 eyes in group 1 and 21 eyes in group 2. FD-300 (odds ratio 0.733, 95% CI 0.620-0.867, P < 0.001) and perifoveal leakage (odds ratio 1.064, 95% CI 1.007-1.124, P = 0.027) were significantly associated with suboptimal clinical course. Area under curve (AUC) was 0.820 for FD-300 and 0.723 for perifoveal leakage in predicting clinical course. FD-300 was negatively correlated with perifoveal leakage (coefficient = -0.325, P = 0.014). Conclusions: Compromised foveal microvascular integrity, represented by lower FD-300 and more severe perifoveal fluorescein leakage, was associated with suboptimal clinical course in anti-VEGF treatment for DME. A negative correlation between FD-300 and perifoveal leakage existed.

Changes in Intraocular Pressure During Hemodialysis: A Meta-analysis.

PRCIS: Acetate dialysate causes elevation of intradialytic intraocular pressure (IOP) and contributed to the rise of IOP in the early years of hemodialysis (HD). Glaucoma, narrow-angle, or impaired aqueous outflow is another moderator causing a rise of intradialytic IOP. PURPOSE: Severe IOP elevation during HD has been described in many case reports. However, the results of primary studies are conflicting. This meta-analysis examined the impact of HD on IOP and explored the potential moderators. METHODS: Medline, PubMed, Embase, Web of Science, and Cochrane were systematically searched. Before-after studies reporting the change of IOP during HD were included. Intradialytic IOP changes were calculated based on 4 different definitions: highest-baseline, lowest-baseline, max-baseline, and end-baseline IOP difference. Standardized mean difference (SMD) was pooled using the random-effects model. RESULTS: Fifty-three studies involving 1903 participants and 2845 eyes were included. Overall data pooling showed no significant rise in intradialytic IOP. However, subgroup analysis showed an intradialytic IOP rise before 1986 (SMD: 0.593; 95% confidence interval: 0.169-1.018; max-baseline IOP difference as representative; most studies using acetate dialysate), no change between 1986 and 2005 (using both acetate and bicarbonate), and a decline after 2005 (SMD: -0.222; 95% confidence interval: -0.382 to -0.063; entirely using bicarbonate). Multivariable meta-regression showed only the type of dialysate, but not publication year or other potential factors, as a significant moderator. Glaucoma was found to be another significant moderator independent of the dialysate effect in bivariate meta-regression. CONCLUSIONS: IOP elevation in the early years of HD with the use of acetate dialysate is less of a clinical problem following its substitution with bicarbonate dialysate. However, physicians should still be cautious of potential IOP changes in the HD population with glaucoma.

Optical Coherence Tomography Angiography Vessel Density Changes in Normal-tension Glaucoma Treated With Carteolol, Brimonidine, or Dorzolamide.

PRECIS: In patients with normal-tension glaucoma (NTG), topical dorzolamide might enhance the vessel density (VD), topical carteolol decreased the VD in the inferior-temporal peripapillary retina, whereas topical brimonidine did not change the VD. PURPOSE: Topical antiglaucoma medications may improve ocular perfusion pressure or microcirculation in the optic nerve head. The study evaluated responses of retinal VD to topical carteolol, brimonidine, and dorzolamide in NTG using optical coherence tomography angiography. PATIENTS AND METHODS: This is a retrospective, nonrandomized, comparative study. The study included 131 individuals (77 men, 54 women) diagnosed with NTG, without systemic medication use, who visited the glaucoma clinic of Chang Gung Memorial Hospital, Taiwan, between January 2019 and May 2020. If both eyes were diagnosed with NTG, only the right eye was included. Of these, there were 80 carteolol-treated eyes, 27 brimonidine-treated eyes, and 24 dorzolamide-treated eyes. We studied the response of optical coherence tomography angiography parameters and retinal nerve fiber layer (RNFL) thickness to drugs, 6 months after treatment. RESULTS: In dorzolamide-treated eyes, increases in the peripapillary superficial retinal VD, especially in the superior-nasal area, were significant; however, no RNFL thickness changes were observed. In contrast, the superficial retinal VD decreased at the inferior-temporal peripapillary area, and RNFL thickness decreased in the inferior-nasal peripapillary area of carteolol-treated eyes. Finally, in brimonidine-treated eyes, changes in either VD parameters or RNFL thickness were not significant. CONCLUSIONS: Topical dorzolamide possibly enhanced the VD of the peripapillary retina in NTG eyes. On the contrary, topical carteolol possibly decreased VD in the inferior-temporal peripapillary retina. Finally, in cases treated with topical brimonidine, peripapillary microcirculation remained unchanged. The study shows preliminary results and future large-scale studies are needed to confirm findings.

Role of growth factors and internal limiting membrane constituents in müller cell migration.

This study investigated the effects of growth factors and internal limiting membrane components on Müller cell migration. We studied the effects of epidermal growth factor (EGF), fibroblast growth factor (FGF), somatomedin (IGF-1), platelet derived growth factor (PDGF), and stromal cell-derived factor-1 alpha (SDF-1α) as well as collagen IV, laminin, and fibronectin on the proliferative and migratory activities of rat Müller cells in vitro. A water soluble tetrazolium-1 assay was used to quantify the viability of Müller cells in respective cultures, and analysis was performed using an enzyme-linked immunosorbent assay reader. All the factors examined had significant proliferative effects on cultured Müller cells (p < .05). A two-well Ibidi silicone culture insert was used to assess Müller cell migration. Müller cells cultured in EGF, FGF, IGF-1, collagen IV, and laminin but not in SDF, PDGF, or fibronectin effectively increased the cell migratory activity (p < .001). In addition, combined EGF and collagen IV, combined FGF and collagen IV, and combined IGF-1 and laminin exhibited more significant (p < .001) effects on Müller cell migration compared with culture a single factor. In summary, this study revealed the combinatorial effects of various growth factors and individual internal limiting membrane constituents. This may assist Müller cell migration together with the macular hole healing process.

Correlation of Visual Field With Peripapillary Vessel Density Through Optical Coherence Tomography Angiography in Normal-Tension Glaucoma.

Purpose: To investigate the retinal vessel density (VD) in healthy and normal-tension glaucoma (NTG) eyes through optical coherence tomography angiography (OCTA) and to determine the correlation between VD and the retinal nerve fiber layer (RNFL) thickness and functional visual field (VF) defects for different locations. Methods: A total of 74 NTG eyes and 24 healthy eyes were included. OCTA VD at 4.5 × 4.5 mm peripapillary region and 3.0 × 3.0 mm macula area, RNFL thickness, and VF pattern deviation results were individually analyzed on the basis of the Garway-Heath sectorization. Correlations between VD and VF/RNFL and VF were compared. Results: In the NTG group, peripapillary VD, superficial macula VD, RNFL thickness, and ganglion cell complex thickness were significantly lower. In the whole peripapillary area and inferotemporal sector, anatomic correlations between VD and VF pattern deviation values were significantly higher than those between the RNFL thickness and VF values. In the subgroup analysis, VD was anatomically correlated with VF in early-, moderate-, and severe-stage NTG eyes, whereas the RNFL thickness was correlated with VF in moderate- and severe-stage NTG eyes. Conclusions: We observed VD reduction in the peripapillary retina and superficial macula area in NTG eyes. The microvascular dropout of VD in the peripapillary retina, especially in the inferotemporal sector, provided a more accurate anatomic correlation with functional VF defects than that of the RNFL thickness, especially in early-stage NTG eyes. Translational Relevance: In patients who cannot comply VF exam, VD is a good tool for disease detection.