Long-Term Visual Outcomes of Primary Congenital Glaucoma in China.

INTRODUCTION: The aim of this study was to investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤21 mm Hg). METHODS: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best corrected visual acuity (VA). Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased VA (<20/50) were also analyzed. RESULTS: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ± 0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60-20/200) in 30%, and poor (<20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11-21.16, p = 0.035) was significantly associated with visual impairment. CONCLUSION: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients.

Evaluation of the genetic association between early-onset primary angle-closure glaucoma and retinitis pigmentosa.

Primary angle-closure glaucoma (PACG) and retinitis pigmentosa (RP) can co-occur, but the mechanism of their association is not yet established. The purpose of this study was to investigate the differences in ocular biometry parameters and molecular genetics in patients with PACG with or without RP, and to determine the association between PACG and RP. Patients with early-onset PACG (age of onset <45 years) with or without RP were selected from the glaucoma outpatient department after full ocular examinations by the same glaucoma specialist (LX). Ocular biometry parameters were statistically analyzed. Blood samples were collected from the probands, and genomic DNA was sent out for whole exome sequencing. Variants in 326 selected genes, were extracted from the whole exome sequencing data and filtered using multiple bioinformatics analysis. The 326 genes included 10 PACG-associated genes from two genome wide association studies; 45 genes associated with anterior segment dysgenesis, microcornea, and microphthalmia; and 271 RetNet genes. Potential pathogenic variants (PPV) were obtained and underwent further genotype-phenotype analysis. As a result, a total of 32 probands with early-onset PACG were collected; nine had accompanying RP. No significant differences were noted for ocular biometry parameters between patients with PACG with RP and with PACG alone. Systematic analysis of the variants revealed that 16 of 32 probands (50%) carried PPV in 15 of 326 genes, including 14 RetNet genes and one anterior segment dysgenesis-associated gene. Of these 16 probands with PPV, five (55.56%) were from the group of nine probands with both had PACG and RP and 11 (47.83%) were from the group of 23 probands with PACG alone. Of the 15 genes, five genes, CRB1, COL2A1, RHO, RP1L1, and PAX6, were reported to cause phenotypes including glaucoma. The variants in RetNet genes appeared to be associated with a significant proportion of PACG, especially in probands with both PACG and RP. These findings enrich the phenotype spectrum of RetNet genes and provide clues for genetic screening for glaucoma. Our study suggests a genetic association between PACG and RP, although the cause-effect relationship between them needs further validation.

Reproducibility of Foveal Avascular Zone and Superficial Macular Retinal Vasculature Measurements in Healthy Eyes Determined by Two Different Scanning Protocols of Optical Coherence Tomography Angiography.

PURPOSE: To assess the reproducibility of quantitative measurements of the foveal avascular zone (FAZ) and retinal vasculature determined by different scanning protocols of optical coherence tomography angiography (OCTA) in healthy volunteers. METHOD: All participants were scanned by two trained operators using an AngioPlex OCTA. Both angiography protocols (6 × 6 mm and 3 × 3 mm) were performed three times on the same eye by operator A and one additional time by operator B. The FAZ area and perimeter, retinal vessel length density (VLD) and perfusion density (PD) of different regions were analysed. RESULTS: Fifty-two eyes from 52 subjects were recruited for this study. The repeated measurements of FAZ, VLD, and PD parameters obtained by the same operator, as well as by different operators, were not significantly different when the same protocol was used (p > 0.05). The intra- and inter-operator intraclass correlation coefficients (ICCs) of the FAZ and central VLD and PD parameters (range, 0.99-0.95) were better than the intra- and inter-operator ICCs of VLD and PD in the inner and outer rings (range, 0.86-0.90). The FAZ area, perimeter, and VLDs obtained by the 3 × 3 mm protocol were larger than those obtained by the 6 × 6 mm protocol (p < 0.01), but the PDs obtained by the 3 × 3 mm protocol were smaller than those obtained by the 6 × 6 mm protocol (p < 0.001). All of the corresponding parameters obtained by the two protocols were positively correlated (r = 0.64-0.99, p < 0.001). CONCLUSION: Both the 6 × 6 and 3 × 3 mm protocols of the AngioPlex OCTA provide good reproducibility for assessing the FAZ and superficial retinal vasculature. However, the values obtained by these different protocols cannot be compared directly.

Damage to the Blood-Aqueous Barrier in Ocular Blunt Trauma and Its Association with Intraocular Pressure Elevation.

BACKGROUND: The aim of this study is to provide a quantitative evaluation of the blood-aqueous barrier (BAB) in patients with ocular blunt trauma and evaluate its association with intraocular pressure (IOP) elevation. METHODS: This is a prospective case-control study, and the following 3 groups were included: elevated IOP (45 patients with an elevated IOP secondary to ocular blunt trauma), normal IOP (27 patients with a normal IOP after ocular blunt trauma), and healthy controls. The main outcome measures were IOP and BAB function evaluated using a laser flare-cell meter (LFCM). RESULTS: Patients had significantly higher flare intensities and cell counts than the normal controls (both p < 0.001), and the elevated-IOP group displayed even higher LFCM readings than the normal-IOP group. Aqueous flare and cell readings were positively correlated with IOP (r = 0.529 and 0.590, respectively, p < 0.001). LFCM readings in the elevated-IOP group were still significantly high even on postraumatic day 120 following anti-inflammatory treatment. CONCLUSION: BAB dysfunction occurred following ocular blunt trauma. Eyes with an elevated IOP displayed a more seriously disturbed BAB and a longer recovery course. Examination with a LFCM provides insight into the pathophysiology of IOP elevation and assists in making decisions concerning anti-inflammatory treatment during follow-up.

RETINAL AND CHOROIDAL CHANGES OF NANOPHTHALMIC EYES WITH AND WITHOUT SECONDARY GLAUCOMA.

PURPOSE: To analyze the retinal and choroidal changes and their relationship in nanophthalmic eyes quantitatively and to evaluate the influence of axial length (AL) and secondary glaucoma on the retina and choroid in these eyes. METHODS: Thirty-seven eyes of 19 nanophthalmic patients (23 eyes with secondary glaucoma, SG group; 14 eyes without secondary glaucoma, NG group) and 38 eyes of 38 age/sex-matched controls were recruited. The retinal and choroidal changes, the foveal retinal thickness (FRT), and the subfoveal choroidal thickness (SFCT) were measured by enhanced depth imaging optical coherence tomography (EDI-OCT, Heidelberg). The parameters were compared between nanophthalmic eyes and controls, as well as between the NG and SG group. The relationship between AL and FRT, AL and SFCT, and FRT and SFCT were analyzed. RESULTS: The optical coherence tomography images revealed broadened outer nuclear layer, and aberrant preservation of the inner retinal layer to different extents existed in the fovea in all nanophthalmic cases. The ganglion cell layer was found much thinner in the SG group than that of the NG group. The low-reflective areas near the outer border of the choroid in nanophthalmic eyes seemed larger than that of controls. The average FRT and SFCT of the total nanophthalmic cases were significantly thicker than those of controls (P < 0.001, P < 0.001, respectively). The FRT of the SG group was thinner than that of the NG group (P < 0.001). No significant difference was found between the SG group and NG group in SFCT (P = 0.83). Axial length was negatively related to FRT and SFCT (P < 0.001, P < 0.001, respectively). The foveal retinal thickness and SFCT were positively related (P = 0.02). CONCLUSION: Retina and choroid are thickened accordantly in nanophthalmic eyes and are negatively related to AL. Secondary glaucoma could affect the FRT but would do nothing to the SFCT. The combined measurement of retina and choroid by enhanced depth imaging optical coherence tomography provides valuable information to facilitate comprehensive understanding of the pathology of nanophthalmos and its complications in vivo.

[Fundus features of nanophthalmos analyzed by optical coherence tomography].

OBJECTIVE: To observe the fundus features of nanophthalmos with or without secondary glaucoma using spectral domain optical coherence tomography (SD-OCT). METHODS: It was a retrospective case-series study. Twenty-three eyes of 12 patients (6 female, 6 male) who were clinically identified to be nanophthalmos (axial length ≤ 20.0 mm) in Zhongshan Ophthalmic Center from June 2008 to December 2010 and twenty-three eyes of 23 age and sex matched normal controls were included in this study. All patients underwent ophthalmological examinations including best-corrected visual acuity, refraction, slit-lamp biomicroscopy and fundus examination, Goldmann applanation tonometry, A-scan and B-scan ultrasound examinations, ultrasound biomicroscopy, fundus photography and spectral domain optical coherence tomography (SD-OCT). All examinations were carried out with natural pupil. The fundus features detected by OCT were compared between nanophthalmos and normal controls, and among nanophthalmos with or without secondary glaucoma.Independent-samples t test was used to analyze the difference of retinal thickness between nanophthalmoic eyes and controls and also between nanophthalmoic eyes with and without secondary glaucoma. Pearson correlation analysis was used to analyze the correlation between axial length and macular retinal thickness. RESULTS: The average age of 12 patients was (25.0 ± 13.1) years, and the mean axial length was (17.30 ± 1.66) mm. Thirteen eyes suffered from secondary glaucoma because of angle closure with average intraocular pressure (IOP) of (28.62 ± 9.18) mm Hg (1 mm Hg = 0.133 kPa). The average IOP of the other 10 eyes without secondary glaucoma was (14.96 ± 3.21) mm Hg.OCT images revealed thickening of the retina in macular fovea, with residual retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, outer plexiform layer, and broadened outer nuclear layer in 23 eyes with nanophthalmos. Pre-retinal folds were seen in 5 eyes with macular cysts.Shallow serous retinal detachment was found in 3 eyes, 2 of which showed focal thickening of retinal pigment epithelium as leopard spots. The cup were not obvious and retina around optic nerve head was thickened in 10 eyes without secondary glaucoma and 4 eyes with secondary early glaucoma, which seemed to be pseudopapilloedema. The other 9 eyes with secondary late glaucoma revealed enlarged cup . The mean macular foveal thickness of nanophthalmic eyes[ (335.65 ± 91.45) µm] was significantly thickened than normal control group [(192.72 ± 11.18) µm] (t = 10.50, P = 0.000) . The mean macular foveal thickness of nanophthalmos with glaucoma [(323.70 ± 104.09) µm] was thinner than those without glaucoma [(403.50 ± 130.24) µm] (t = 3.50, P = 0.002). Macular foveal thickness were negatively related with axial length in both nanophthalmos with and without secondary glaucoma (R = -0.797, P = 0.001). CONCLUSIONS: Macular hypoplasia and crowded optic nerve head are two important characteristic of fundus appearances in nanophthamos.SD-OCT can clearly reveal the changes of macular retina and optic nerve head. SD-OCT will be a very useful tool to help diagnose nanophthamos and evaluate its possible complications.

[Detection of the anterior segment configuration of primary angle-closure glaucoma by anterior segment optical coherence tomography].

OBJECTIVE: To quantitatively measure and evaluate the ocular anterior segment parameters in different subtypes of primary angle-closure glaucoma (PACG) using anterior segment optical coherence tomography (AS-OCT). METHODS: This retrospective study collected Fifty-five subjects (55 eyes) with APACG, 63 (63 eyes) with chronic primary angle-closure glaucoma (CPACG) and 90 (90 eyes) normal controls from December 2009 to December 2010 in Zhongshan Ophthalmic Center. AS-OCT examination was performed on all patients and the anterior segment parameters were recorded including: central anterior chamber depth (ACD), anterior chamber width (ACW), anterior chamber volume (ACV), angle opening distance (AOD), trabecular iris area (TISA), angle recess area (ARA), lens thickness (LT) and crystalline lens rise (CLR). The differences of parameters between APACG, CPACG and normal controls were compared. RESULTS: The anterior segment parameters of APACG and CPACG were significantly (P ≤ 0.001) smaller, respectively, than those of normal controls (PACG: ACD 1.81 ± 0.25 mm, ACW 11.30 ± 0.43 mm, AOD 0.039 mm, ARA 0.038 mm(2), ACV 72.8 ± 16.04 mm(3), TISA 0.017 mm(2), Mean ± SD, and CPACG: ACD 2.02 ± 0.25, ACW 11.49 ± 0.45, AOD 0.042, ARA 0.053, ACV 83.60 ± 19.49, TISA 0.022 vs. normal: ACD 2.70 ± 0.35, ACW 11.81 ± 0.47, AOD 0.260, ARA 0.197, ACV 148.52 ± 31.89, TISA 0.100). The LT and CLR of PACG were significantly (P < 0.001) larger, respectively, than that of normal controls (LT: APACG 5.22 ± 0.38, CPACG 5.06 ± 0.36 mm, CLR: APACG 1.07 ± 0.26, CPACG 0.94 ± 0.21 mm vs. normal: LT 4.57 ± 0.42, CLR 0.39 ± 0.33 mm). Compared with CPACG, the anterior segment parameters of APACG were significantly (P < 0.001 - 0.015) decreased, but the LT (P = 0.003) and CLR were significantly (P < 0.001) increased. Compared with APACG-fellow eyes, the anterior segment parameters of APACG-attacked eyes were significantly (P < 0.001 - 0.041) decreased (Fellow-eye: ACD 1.90 ± 0.23 mm, AOD 0.045 mm, TISA 0.037 mm(2), ARA 0.047 mm(2) vs. attached-eye: ACD 1.81 ± 0.25, AOD 0.039, TISA 0.017 and ARA 0.038), while CLR was significantly (t = 1.349, P = 0.043) increased (fellow-eye: 1.01 ± 0.23 mm vs. Attached-eye: 1.07 ± 0.26). There was no significant difference in the other AS-OCT parameters between APACG-attacked eyes and fellow eyes (t = 0.574 - 1.147, P = 0.257 - 0.567). CONCLUSIONS: Our results indicated a more crowding anterior segment configuration in PACG than that in normal controls and a more anterior located and thicker lensing APACG than that in CPACG, which constitute a morphological basis of acute attack.

[Protection effect of sodium hyaluronate on ocular surface toxicity induced by Benzalkonium chloride-preserved brimonidine in rabbits].

OBJECTIVE: To investigate the protective effects of sodium hyaluronate on ocular surface toxicity induced by a prolonged use of benzalkonium chloride-preserved Brimonidine eye drops. METHODS: Experimental study. Thirty adult female New Zealand rabbits were divided into three groups with randomized numbers design. Ten rabbits were treated with 0.2% Brimonidine eye drops and PBS (PBS group), the other ten rabbits with 0.2% Brimonidine combined with sodium hyaluronate eye drops (SH group), and control group received no treatment for 60 days. Schirmer test, fluorescein (FL) and Rose Bengal (RB) staining, conjunctival impression cytology specimens collecting were performed on day 0, 31, and 61. Apoptosis of conjunctival epithelium was detected by in situ terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay on day 61. Conjunctival inflammation was observed by hematoxylin eosin staining. Histomorphological changes of cornea and conjunctiva were observed by light microscopy, and scanning and transmission electron microscopy at day 61. Fluorescein and Rose Bengal scores were analysed by Kruskal-Wallis test. Schirmer scores, goblet cell density and inflammatory cells infiltration were analysed by repeated measures analysis of variance. RESULTS: There were significant differences in fluorescein and Rose bengal (H = 22.031, 15.303, P < 0.01) staining among the groups on day 61. Compared with the control group (FL: 0, 0-1, RB: 0, 0-1), fluorescein and Rose Bengal scores were significantly (P < 0.001) increased in PBS group (FL: 1.5, 1-2, RB: 1, 1-2), whereas was significantly (P < 0.001) decreased in SH group (FL:0, 0-1 RB:1, 0-1) when compared to PBS group. There were significant differences in aqueous tear production and goblet cell density (F = 7.980, 14.545, both P < 0.01) among the groups on day 61. Compared with the control group [(9.43 ± 0.57) mm, (87.73 ± 2.34/HP)], Schirmer scores and goblet cell density were significantly (P < 0.01) reduced in PBS-treated group [(6.61 ± 0.38) mm, (68.06 ± 3.61)/HP], but significantly (P < 0.05) increased in SH-treated group [(8.75 ± 0.57) mm, (82.31 ± 1.64)/HP] compared with PBS-treated group. The number of inflammatory cells was significant difference (F = 56.306, P < 0.001) among the groups on day 61. Compared with the control group [(39.89 ± 2.03)/HP], inflammatory cells infiltration was significantly (P < 0.01) increased in both PBS [(73.18 ± 2.17)/HP] and SH groups [(48.79 ± 2.64)/HP], however, SH-treated group was significantly lowered when compared with PBS-treated group. In addition, decrease in apoptosis, complete microvilli and cell organelles were found in the corneal and conjunctival epithelial cells in SH-treated group. CONCLUSIONS: Our results demonstrate that topical application of SH reduces the ocular toxicity and protect the ocular surface in the long term anti-glaucomatous medical therapies and may be considered as a vehicles or neutralizing material for future ocular application.

INVERSE SOURCE PROBLEM FOR ACOUSTICALLY-MODULATED ELECTROMAGNETIC WAVES.

We propose a method to reconstruct the electrical current density from acoustically-modulated boundary measurements of time-harmonic electromagnetic fields. We show that the current can be uniquely reconstructed with Lipschitz stability. We also report numerical simulations to illustrate the analytical results.

Microcatheter-Assisted Circumferential Trabeculotomy After Failed Glaucoma Surgeries in Childhood Glaucoma.

PURPOSE: To evaluate the outcomes of microcatheter-assisted trabeculotomy (MAT) in childhood glaucoma (primary congenital glaucoma [PCG], juvenile open-angle glaucoma [JOAG], and secondary childhood glaucoma [SCG]) after failed glaucoma surgery. DESIGN: Retrospective interventional case series. METHODS: Patients with childhood glaucoma who underwent MAT after failed glaucoma surgery with at least 12 months of follow-up were evaluated. Pre- and postoperative intraocular pressure (IOP) and the number of glaucoma medications were recorded and compared. Success was defined as an IOP ≤21 mm Hg with or without glaucoma medication. Analysis of variance was used to compare the glaucoma subgroups. RESULTS: Forty-five eyes (42 patients) with a median follow-up period of 19 months were included. The median age at the time of MAT was 10 (range, 0.8-33) years. The mean number of previous surgeries was 1.3 ± 0.5. The IOP had significantly reduced from baseline in all PCG, JOAG, and SCG patients (27.9 ± 4.5 vs 16.3 ± 8.0 mm Hg, P = .001; and 30.8 ± 9.4 vs 13.5 ± 3.0 mm Hg, P < .001; and 31.5 ± 7.1 vs 16.5 ± 5.3 mm Hg, P = .001, respectively). Fewer glaucoma medications were needed after MAT in all 3 groups (each P < .001). At the last visit, the total success rates in PCG, JOAG, and SCG were 93.8%, 100%, and 88.9%, respectively. No severe complications were observed. CONCLUSION: MAT can effectively manage PCG, JOAG, and SCG after failed surgeries, providing successful outcomes and no serious complications. Following failed glaucoma surgeries, MAT may offer these patients with childhood glaucoma an excellent opportunity to achieve IOP control.

Inhibition of p38 mitogen-activated protein kinase phosphorylation decrease tert-butyl hydroperoxide-induced apoptosis in human trabecular meshwork cells.

PURPOSE: Oxidative stress induced trabecular meshwork cells death is believed to be involved in the pathogenesis and progression of primary open-angle glaucoma (POAG). However, the intrinsic mechanism is yet to be clarified. This study is to investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in tert-butyl hydroperoxide (tBHP)-induced apoptosis of human trabecular meshwork (iHTM) cells. METHODS: The human trabecular meshwork cells were treated with tBHP for 1 or 2 h with or without pretreatment of SB203580, an inhibitor of MAP kinase homologs. Cell viability was analyzed using 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2h-tetrazolium bromide assay. Reactive oxygen species (ROS) levels were determined using dihydrodichlorofluorescein staining, and the chymotrypsin-like protease activities were measured using the Suc-LLVY-aminoluciferin substrate. Cell apoptosis was analyzed by Hoechst 33258 staining and annexin V-PI labeling. The protein level of phospho-p38 was measured using western blot analysis. RESULTS: The intracellular ROS increased more than 50 fold and more than 100 fold after tBHP exposure for 1 h and 2 h, respectively (p<0.05). However, there was no difference in ROS levels between SB203580(-) and SB203580(+) cells (p>0.05). In 1 h tBHP treatment group, the cell viability was significantly improved in SB203580(+) cells (81.08%±1.93%) compared to the SB203580(-) cells (69.35%±1.52%), the chymotrypsin-like proteasome inactivation decreased in SB203580(+) cells (60.94%±0.55%) compared to the SB203580(-) cells (70.59%±0.88%), and apoptosis was impoved in SB203580(+) cells (12.75%±1.91%) compared to the SB203580(-) (28.23%±3.23%) (p<0.05). In 2 h tBHP treatment group, cell viability improved in SB203580(+) cells (76.72%±2.11%) compared to SB203580(-) cells (57.88%±2.20%), chymotrypsin-like proteasome inactivation was improved in SB203580(+) cells (62.99%±0.41%) compared to SB203580(-) cells (74.93%±0.54%), and apoptosis was improved in SB203580(+) cells (20.40%±3.44%) compared to SB203580(-) cells (39.20%±5.91%) (p<0.05). Phosphorylation of p38MAPK was significantly increased after tBHP exposure in SB203580 (-) cells and decreased sharply in SB203580(+) cells than that of control group (p<0.05). While there was no difference on the original form of p38MAPK among SB203580(-) and SB203580(+) cells after tBHP exposure and control group (p>0.05). CONCLUSIONS: Activation of p38MAPK plays an important role in tBHP-induced apoptosis of iHTM cells. Further study on the mechanisms of p38MAPK in human TM cell apoptosis may help to illuminate the pathogenesis of POAG.

[The efficacy of Ahmed glaucoma valve implantation in the management of early stage of glaucoma secondary to blunt ocular trauma].

OBJECTIVE: To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) implantation in the early stage of glaucoma secondary to contusion injuries. METHODS: A retrospective case series study. The study was made in 29 consecutive patients with glaucoma secondary to blunt trauma who were uncontrolled by multiple medications and then performed AGV implantations in less than 2 months after the trauma. The duration from injury to IOP elevation was 1 to 30 (6.10 ± 1.13) days. The time from injury to AGV implantation was 16 to 60 (40.03 ± 2.97) days. The patients were followed-up for a period of 6 to 42 (20.75 ± 1.66) months. The main outcome measures included intraocular pressure (IOP), visual acuity (VA), number of glaucomatous medications, intra- and postoperative complications. IOPs were analyzed by repeated measures analysis of variance, numbers of medication assessed by Kruskal-Wallis rank sum test followed by Bonferroni test, and VA comparison was performed using paired Student t-test. RESULTS: The absolute success rate was 86.21% and the conditional success rate was 13.79% after AGV implantation. Compared with pre-operation, the IOP was significantly(F = 124.09, P < 0.05) lowered at the last following-up of post-operation(42.59 ± 1.82)vs (15.12 ± 0.56) mm Hg(1 mm Hg = 0.133 kPa), the numbers of glaucomatous medications were significantly (H = 131.73, P < 0.05) reduced post-operatively (3.93 ± 0.15) vs (0.21 ± 0.12) species, and the VA was significantly (t = -3.466, P < 0.05) improved post-operatively (logMAR 0.40 vs logMAR 0.70). Two cases with shallow anterior chamber and three cases with hyphema were observed in the early stage after the surgery. No persistent hypotony, tube exposure or other serious complications were noted. CONCLUSION: AGV implantation is safe and effective in the management of intractable secondary glaucoma at early stage of contusion injuries.

Longitudinal Changes in Peripapillary Retinal Nerve Fiber Layer and Macular Ganglion Cell Inner Plexiform Layer in Progressive Myopia and Glaucoma Among Adolescents.

Purpose: This study aimed to investigate the differences in longitudinal changes in the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell plus inner plexiform layer (GCIPL) caused by progressive myopia and glaucoma among adolescents. Design: This was a retrospective observational study. Methods: A total of forty-seven and 25 eyes of 47 and 25 adolescents with myopia progression (MP) and glaucoma progression (GP), respectively, who were followed up at the Zhongshan Ophthalmic Center for at least 3 years, were included in the study. The pRNFL and GCIPL that measured at the initial and last visits were analyzed. Results: The median follow-up period was 5 years for both two groups. During follow-up, the whole, superior, and inferior pRNFL decreased in both the MP and GP groups, (p < 0.001). Nasal pRNFL decreased in the MP group (p < 0.001) but had no significant difference in the GP group (p = 0.19). Temporal pRNFL was increased in the MP group (p < 0.001) but decreased in the GP group (p < 0.001). The average and sectoral GCIPL decreased in both groups (p < 0.001). The annual change rate of temporal pRNFL and pRNFL at 10-, 8-, 9-, and 7-clock-hour sectors and the inferotemporal GCIPL has better diagnostic value to differentiate glaucoma from myopia (the area under the receiver operating characteristic curve, AUC > 0.85). Conclusion: Glaucoma and MP could cause loss of the pRNFL and GCIPL in adolescents; however, the loss patterns were different between the two groups. The temporal quadrant and 7-, 8-, 9-, and 10-clock-hour sector pRNFL and the inferotemporal GCIPL can help distinguish pRNFL and GCIPL loss caused by glaucoma or MP.

Use of ultrasound biomicroscopy to predict the outcome of anterior segment reconstruction in congenital fibrovascular pupillary membrane with secondary glaucoma.

AIMS: To evaluate the efficacy and safety of anterior segment reconstruction (ASR) in congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG) basing ultrasound biomicroscopy (UBM) classification. METHODS: This ambispective cohort study enrolled patients with CFPMSG who underwent ASR between January 2014 and September 2020. Comprehensive ophthalmic examinations and UBM were performed before surgery and postoperatively. The patients were classified into three types according to the UBM configurations. Anterior chamber recovery (ACR) was defined as deepening in anterior chamber (≥1.5 mm all through final follow-up (FFU), while success following ASR was defined as ACR and intraocular pressure (IOP)≤21 mm Hg. RESULTS: 25 eyes of 25 patients underwent ASR (average age at operation 5.8±5.0 months, 48% girls) with FFU 15.8±16.9 months. Enrolled subjects were classified into type Ⅰ (11 eyes), type Ⅱ (11 eyes) and type Ⅲ (3 eyes). After ASR, 23 eyes (92%) achieved ACR, and the mean ACD increased in all groups (p=0.006, <0.001 and 0.003, respectively). Eyes with types Ⅰ and Ⅱ demonstrated a reduction of IOP (p=0.009 and 0.002, respectively). ASR success rate was highest in type Ⅰ (72.9%) compared with types Ⅱ and Ⅲ (18.2% and 0%, respectively; p=0.011). ASR led to decreased number of antiglaucoma medications for type Ⅰ CFPMSG at FFU (p=0.016). No vision-threatening postoperative complications occurred. CONCLUSIONS: ASR for CFPMSG results in increased ACD and improvement in IOP. Postoperative IOP control was best in type Ⅰ CFPMSG but not as effective in types Ⅱ and Ⅲ. UBM-based classification helps to predict the surgical outcome of ASR in CFPMSG.

Medication Adherence and Common Barriers for Caregivers of Preschool Children with Pediatric Glaucoma.

Purpose: To investigate the medication adherence among caregivers of preschool children with pediatric glaucoma and to elucidate common barriers leading to poor adherence. Methods: A cross-sectional study. Caregivers of preschool children with pediatric glaucoma completed a questionnaire on demographic information of caregivers, demographic and disease characteristics of children, caregivers-reported medication adherence (by an adapted Morisky Adherence Scale), and possible 13 barriers. Results: Overall 132 questionnaires were considered valid. Thirty-six percent of all reported poor medication adherence. Caregivers' age and self-evaluated knowledge about pediatric glaucoma showed a significant difference between the adherent and nonadherent groups (P < 0.05). Nineteen percent of all reported only one barrier as important, 65% cited multiple barriers, and 16% cited no barriers. Anxiety and depression were cited as important by most caregivers in both groups. Univariate logistic regression analysis demonstrated that difficulty with the acquisition of medications (OR, 2.5; 95% CI, 1.1-5.7; P=0.025), difficulty with medication schedule (OR, 2.3; 95% CI, 1.0-5.0; P=0.043), and high expenses for medications (OR, 4.8; 95% CI, 1.4-15.9; P=0.011) were significantly associated with higher odds of poor adherence. Conclusions: Over one-third of caregivers of preschool children with pediatric glaucoma were in poor medication adherence. Nearly two-thirds of caregivers cited multiple barriers simultaneously as important hindrances to medication usage. Anxiety and depression, difficulty with the acquisition of medications, difficulty with the medication schedule, and high expenses for medications were prominent barriers. Individualized solutions should be provided according to reported barriers by each caregiver and the other most common barriers.

Effect of Combined Surgery in Patients with Complex Nanophthalmos.

(1) Background: To evaluate the efficacy and safety of combined surgery (limited pars plana vitrectomy, anterior-chamber stabilized phacoemulsification, IOL implantation and posterior capsulotomy, LPPV + ACSP + IOL + PC) in complex nanophthalmos. (2) Methods: Patients with complex nanophthalmos were recruited to undergo LPPV + ACSP + IOL + PC from January 2017 to February 2021. Preoperative and post-operative intraocular pressure (IOP), best corrected visual acuity (BCVA), anterior chamber depth (ACD), and number of glaucoma medications were compared using the paired t-test or Wilcoxon signed rank sum tests. Surgical success rate was evaluated. Surgery-associated complications were documented. (3) Results: Forty-five eyes of 37 patients with complex nanophthalmos were enrolled. The mean follow-up period was 21.7 ± 10.6 months after surgery. Mean IOP decreased from 32.7 ± 8.7 mmHg before surgery to 16.9 ± 4.5 mmHg (p < 0.001) at the final follow-up visit, mean logMAR BCVA improved from 1.28 ± 0.64 to 0.96 ± 0.44 (p < 0.001), mean ACD significantly increased from 1.14 ± 0.51 mm to 3.07 ± 0.66 mm (p < 0.001), and the median number of glaucoma medications dropped from 3 (1, 4) to 2 (0, 4) (p < 0.001). The success rate was 88.9% (40 eyes) at the final follow-up visit. Two eyes had localized choroidal detachments which resolved with medical treatment. (4) Conclusions: LPPV + ACSP + IOL + PC is a safe and effective surgical procedure, which can decrease IOP, improve BCVA, deepen the anterior chamber, and reduce the number of glaucoma medications in patients with complex nanophthalmos. It can be considered as one of the first treatment in nanophthalmic eyes with complex conditions.

[Comparison of anterior segment changes before and after laser peripheral iridectomy by anterior segment optical coherence tomography in eyes with primary acute angle closure glaucoma].

OBJECTIVE: To evaluate the changes of anterior segment configuration after surgical peripheral iridectomy (SPI) in patients with primary acute angle closure glaucoma (PAACG) by using anterior segment optical coherence tomography (AS-OCT). METHODS: This retrospective self control study consisted of thirty-seven eyes of 37 patients with PAACG who were consecutively recruited in Zhongshan Ophthalmic Center. The peripheral anterior synechiae (PAS) of these patients was less than 5 clock time point. Central anterior chamber depth (ACD), angle opening distance (AOD), trabecular iris area (TISA), angle recess area (ARA), anterior chamber width (ACW), anterior chamber volume (ACV), and crystalline lens rise (CLR) were measured using AS-OCT before and one month after SPI. RESULTS: After SPI, AOD (0.125 ± 0.072) µm, TISA (0.091 ± 0.041) mm(2), ARA (0.095 ± 0.042) mm(2), ACA (14.230 ± 2.000) mm(2) and ACV (90.074 ± 16.796) mm(3) were significantly increased compared with before SPI AOD (0.088 ± 0.078) µm, TISA (0.050 ± 0.048) mm(2), ARA (0.059 ± 0.057) mm(2), ACA (12.332 ± 2.457) mm(2), ACV (73.131 ± 16.976) mm(3) (t = -8.015 to 1.066, P = 0.001 to 0.044), respectively. There were no significantly changes in ACD, ACW and CLR (t = -1.505 to 0.516, P = 0.102 to 0.609). CONCLUSIONS: PAACG can be controlled by SPI resulting in an increase of AOD, TISA, ARA, ACA and ACV, but not ACD or CLR.

Surgical outcomes of Ahmed glaucoma valve implantation in patients with glaucoma secondary to iridocorneal endothelial syndrome.

OBJECTIVES: To evaluate the long-term outcome of patients with iridocorneal endothelial (ICE) syndrome who underwent Ahmed glaucoma valve implantation surgery for uncontrolled glaucoma. METHODS: Eighteen patients who suffered from unilateral ICE syndrome with uncontrolled glaucoma and subsequently underwent Ahmed aqueous shunt surgery at Zhongshan Ophthalmic Center between January 2008 and December 2016 were reviewed. Outcome measures included intraocular pressure (IOP), the use of glaucoma medications, visual acuity, further surgical interventions, and surgical complications. RESULTS: The mean IOP was reduced from 34.8 ± 10.6 mmHg on 3.6 ± 0.5 medications to 17.4 ± 4.9 mmHg (t = 6.791, P = 0.000) on 1.6 ± 1.1 medications (Z = -3.545, P = 0.000) at the last follow-up (42.0 ± 19.3 months). Five eyes (27.8%) achieved complete success, nine (50.0%) achieved qualified success, and the remaining four (22.2%) were considered failures. Survival was 94.4% at 1 year, 88.1% at 2 years, and 73.5% at 3 years. Four cases displayed a flat anterior chamber and were treated with a single anterior chamber reformation surgery with no recurrence. No other complications related to the glaucoma drainage implants occurred in this series. CONCLUSIONS: Ahmed glaucoma valve implantation appears to be a safe and effective method for treating glaucoma secondary to ICE syndrome. Postoperative shallow anterior chamber and hypotony may occur but responds well to the treatment. Early consideration may be given to aqueous shunt surgery in patients with glaucoma secondary to ICE syndrome when trabeculectomy fails.

Clinical and Ultrasound Biomicroscopic Characteristics of Congenital Fibrovascular Pupillary Membrane-Induced Secondary Glaucoma.

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG). Design: Cross-sectional case series. Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA. Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I ("U" shape), 34% type II ("Y" shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045). Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an in vivo study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.