Changes in the incidence of optic neuritis before and after COVID-19: A nationwide study 2017-2022.

PURPOSE: To determine the risk of optic neuritis (ON) during non-pharmaceutical interventions (NPI), vaccination and infection phase of coronavirus disease-19 (COVID-19) in comparison to pre-outbreak levels in pediatric and adult populations in South Korea. DESIGN: A nationwide, population-based, retrospective study. PARTICIPANTS: South Korean individuals with a primary diagnosis of ON between January 2017 and December 2022. METHODS: The Korean Health Insurance Review and Assessment database was queried for new diagnoses of ON between January 2017 and December 2022. Data were divided into 4 periods: pre-COVID-19 (2017-2019), NPI (2020), nationwide vaccination (2021) and nationwide infection (2022). The risk of ON development for each period was calculated and compared to pre-COVID-19 levels with 95% confidence intervals (CI) reported. MAIN OUTCOME MEASURES: Incidence rate ratio (IRR) of ON for each period. RESULTS: A total of 7,216 patients (52.7 % females) were included in the study, with 3,770 patients diagnosed with ON pre-COVID-19 (2017-2019), 1,193 patients during NPI, 1,135 patients during the vaccination and 1,118 patients during the infection phases. The annual incidence of ON during NPI (IRR 0.92 (95% CI 0.85-1.00), P=0.043), vaccination (IRR 0.88 (95% CI 0.81-0.95), P=0.001) and infection (IRR 0.86 (95% CI 0.80-0.93), P<0.001) phases significantly decreased compared to pre-COVID-19 levels when adjusted for age and sex. The proportions of diagnosis with multiple sclerosis (MS), neuromyelitis optica (NMO), and acute disseminated encephalomyelitis (ADEM) among patients who developed ON significantly increased in 2021 in comparison to the pre-outbreak levels (9.87% vs. 5.81%; P=0.0002). CONCLUSIONS: The risks of ON development during NPI, vaccination and infection phases of COVID-19 did not increase in comparison to the pre-outbreak levels in general population. However, COVID-19 vaccination may be associated with increased risks of ON associated with diseases such as ADEM, MS and NMOSD.

Baseline intraocular pressure: an independent risk factor in severe steroid-induced ocular hypertension after intravitreal dexamethasone implant.

PURPOSE: To evaluate the baseline intraocular pressure (IOP)-related risk of severe steroid-induced ocular hypertension (SIOH). We hypothesized that the incidence and severity of SIOH may differ according to baseline IOP in patients who received intravitreal dexamethasone implants. METHODS: A total of 889 eyes treated with intravitreal dexamethasone implants and a baseline IOP of ≤ 23 mmHg were enrolled. Enrolled patients were divided into two groups: the steroid-responders (127 eyes) and the non-steroid-responders (762 eyes). The steroid-responders group was subdivided into post-injection IOP of ≥ 25, > 30, or > 35 mmHg or IOP elevation of ≥ 10 mmHg over the baseline value. The odds ratio of SIOH was calculated using univariable logistic regression analysis, and significant variables were analyzed with a multivariable model. IOP was measured before (baseline IOP) and after dexamethasone implant injection at 1 week and 1, 2, 3, 6, and 12 months. RESULTS: Although baseline IOP was significantly associated with the development of SIOH in logistic regression analysis, the results from the subgroup analysis differed. In the group with IOP elevation of ≥ 10 mmHg over the baseline, SIOH was not significantly associated with baseline IOP, but it was significantly related to higher baseline IOP in the severe SIOH group (IOP > 30 and > 35 mmHg). CONCLUSIONS: Higher baseline IOP is a risk factor for severe SIOH. Clinicians should be aware of the risk of SIOH when administering steroids intravitreally to patients with high baseline IOP (IOP > 19 mmHg).

Protective effect of etanercept, an inhibitor of tumor necrosis factor-α, in a rat model of retinal ischemia.

BACKGROUND: To assess the neuroprotective effect of etanercept (Enbrel®) which is a commercialized Tumor necrosis factor-α (TNF-α) inhibitor on axonal injury in an animal model of acute ischemia. METHODS: Acute ischemia was induced by intraocular pressure elevation in 36 rats. The treatment groups underwent subcutaneous injection of etanercept (0.3 or 1.0 mg/kg) three times per week up to 4 weeks. The control groups were treated in the same manner using the same volume of phosphate-buffered saline (PBS). Optic nerve damage was evaluated by counting the number of axons under a transmission electron microscope. Microglial cell activity was assessed using Iba1 and CD68. RESULTS: After induction of ischemia, the ratio of preserved axons was significantly greater in the 2-week 1.0-mg/kg etanercept-treated group than in the PBS-treated group (p = 0.062). The 4-week 0.3-mg/kg and 1.0-mg/kg etanercept-treated groups also showed significantly higher ratios of preserved axons than did the PBS-treated group (p = 0.021 and 0.003, respectively). The expression of Iba1 and CD68 in the optic nerve was lower in the etanercept-treated groups than in the PBS-treated groups. Immunohistochemical staining using rabbit anti-Iba1 antibody showed that the amount of microglia at the optic nerve head was noticeably lower in the etanercept-treated groups than in the PBS-treated groups. CONCLUSIONS: Etanercept significantly suppressed optic nerve injury in this rat model of acute ischemia. This in vivo study suggests that etanercept might be a novel neuroprotective treatment agent for TNF-α-related disease.

Tear Lipid Layer Thickness Change and Topical Anti-Glaucoma Medication Use.

PURPOSE: To investigate the effects of topical anti-glaucoma medications on tear lipid layer thickness (LLT) and the ocular surface. METHODS: This retrospective study examined ocular surface disease (OSD) subjects who had (n = 34) and who did not have (n = 51) open-angle glaucoma (OAG). OSD was evaluated with lipid layer thickness (using LipiView interferometer), tear breakup time (TBUT), total corneal and conjunctival staining (Oxford grading scale), and Ocular Surface Disease Index (OSDI). Four variables (total duration of anti-glaucoma medication use, duration of current anti-glaucoma medication use, total number of daily anti-glaucoma medication drops applied, and total number of anti-glaucoma medications [bottles]) related to anti-glaucoma medication were used to verify associations with LLT. RESULTS: Among the parameters, only LLT showed significantly lower values in the OAG group. In both groups, total staining showed a significant negative correlation between LLT and TBUT. Only in the OAG group, the OSDI showed significant correlations with number of medications (r = 0.389, p = 0.012) and daily number of drops (r = 0.354, p = 0.02); LLT showed significant correlations with TBUT (r = 0.381, p = 0.026) and total medication duration (r = -0.387, p = 0.013). In multivariate analyses, TBUT and total medication duration showed significant correlations with LLT (p = 0.032 and p = 0.015, respectively) in the OAG group. CONCLUSIONS: Topically medicated OAG subjects with OSD had a lower tear LLT than those with OSD who did not have OAG. Therefore, our results indicate that one should evaluate ocular surface disease status in patients who take anti-glaucoma medications.

Effect of trabeculectomy on the accuracy of intraocular lens calculations in patients with open-angle glaucoma.

BACKGROUND: The objective of the study is to examine the effect of trabeculectomy on intraocular lens power calculations in patients with open-angle glaucoma (OAG) undergoing cataract surgery. DESIGN: The design is retrospective data analysis. PARTICIPANTS: There are a total of 55 eyes of 55 patients with OAG who had a cataract surgery alone or in combination with trabeculectomy. METHODS: We classified OAG subjects into the following groups based on surgical history: only cataract surgery (OC group), cataract surgery after prior trabeculectomy (CAT group), and cataract surgery performed in combination with trabeculectomy (CCT group). MAIN OUTCOME MEASURES: Differences between actual and predicted postoperative refractive error. RESULTS: Mean error (ME, difference between postoperative and predicted SE) in the CCT group was significantly lower (towards myopia) than that of the OC group (P = 0.008). Additionally, mean absolute error (MAE, absolute value of ME) in the CAT group was significantly greater than in the OC group (P = 0.006). Using linear mixed models, the ME calculated with the SRK II formula was more accurate than the ME predicted by the SRK T formula in the CAT (P = 0.032) and CCT (P = 0.035) groups. CONCLUSIONS: The intraocular lens power prediction accuracy was lower in the CAT and CCT groups than in the OC group. The prediction error was greater in the CAT group than in the OC group, and the direction of the prediction error tended to be towards myopia in the CCT group. The SRK II formula may be more accurate in predicting residual refractive error in the CAT and CCT groups.

Comparison of three types of images for the detection of retinal nerve fiber layer defects.

PURPOSE: To compare the clinical effectiveness of three types of images for detecting retinal nerve fiber layer (RNFL) defects. METHODS: Three image sets of 100 subjects (9 normal control subjects, 16 glaucoma suspects, and 75 glaucoma patients) were produced using color fundus photography, typical red-free RNFL photography, and blue reflectance RNFL photography with confocal scanning laser ophthalmoscopy (CSLO). A total of 300 images were rated twice in random order by five independent evaluators who were masked to the patient characteristics; each image was rated as normal, having a diffuse RNFL defect, or showing a wedge RNFL defect. Intraobserver and interobserver agreement, sensitivity, specificity, accuracy, and area under the curve were assessed. An additional analysis was performed for identifying differences in two black-and-white RNFL photographs. RESULTS: The results showed high intraobserver agreement, with relatively low interobserver agreements among the five evaluators. Blue reflectance RNFL photography with CSLO demonstrated the best performance in sensitivity, specificity, accuracy, and area under the curve. Blue reflectance RNFL images showed better accuracy than red-free RNFL images especially in subjects with wedge defects and in advanced glaucomatous cases. CONCLUSIONS: The RNFL images produced using blue reflectance with CSLO showed the best performance for the detection of RNFL defects, especially in cases with wedge defects and advanced glaucoma stages.

Visual fields and OCT role in diagnosis of glaucoma.

PURPOSE: To evaluate the clinical performance of visual field (VF) tests and optical coherence tomography (OCT) in diagnosing glaucoma. METHODS: One hundred sets of disc photographs, red-free fundus photographs, VF tests, and OCT images were presented progressively to seven ophthalmologists. Each set was provided in three steps: (1) the disc and red-free fundus photographs were shown first; (2) then, VF tests were also provided; and (3) finally, the OCT results were provided. The same process was repeated on another day. Kappa statistics were used to assess the intraobserver and interobserver agreement, as well as the agreement with the reference standard. RESULTS: The intraobserver agreement was almost perfect in this study and did not change markedly with the addition of diagnostic tools. The interobserver agreement increased from 0.54 to 0.61 when VF was added and increased slightly to 0.63 with OCT. The agreement with the reference standard also increased significantly from 0.48 to 0.61 after adding VF and increased slightly with additional OCT. CONCLUSIONS: An optic disc evaluation and VF test are sufficient to diagnose glaucoma in most cases. However, OCT can play an important role in detecting glaucoma in cases in which it cannot be identified by optic disc examination and VF.

Systemic Arterial Stiffness and Choroidal Microvascular Insufficiency on the Structural Progression of Normal Tension Glaucoma.

PURPOSE: To identify the role of systemic arterial stiffness and choroidal microvascular insufficiency on structural progression of normal-tension glaucoma (NTG). DESIGN: Retrospective cohort study. METHODS: A total of 107 early NTG eyes of 88 patients, who underwent pulse wave velocity (PWV) measurements and optical coherence tomography (OCT) angiography (OCT-A) at baseline, were categorized depending on the presence of peripapillary choroidal microvasculature dropout (MvD) and PWV. Differences in glaucomatous progression were analyzed. Structural progression rates were determined using the trend-based analysis of Cirrus OCT. RESULTS: Thirty-two eyes displayed choroidal MvD (62.7 [95% CI 58.4-67.0] years old, 53.6% males), and 70 eyes did not show any MvD (59.9 (95% CI 57.1-62.6) years old, 53.3% males) at baseline. Patients were followed for 48.4 (95% CI 40.0-56.8) months. When they were further divided based on PWV (high PWV ≥ 1400 cm/sec), those with choroidal MvD and high PWV showed significantly faster thinning in macular ganglion cell-inner plexiform layer (GCIPL; P = .023). In comparison to those with low PWV and no MvD, eyes with high PWV and MvD in the peripapillary area were likely to show fast structural progression (≤-1.2 µm/year) in the macular GCIPL by odds of 6.019 (95% CI 1.619-38.531, P = .025). CONCLUSIONS: In NTG eyes, GCIPL thinning was faster when choroidal MvD and high systemic arterial stiffness were present. The simultaneous presence of regional and systemic vascular insufficiency may be associated with rapid glaucoma structural progression in eyes with low baseline intraocular pressure.

Clinical prediction nomogram for steroid-induced ocular hypertension risk in patients with intravitreal dexamethasone implant.

Background: Recognizing the risk factors and understanding the mechanisms underlying steroid-induced ocular hypertension (SIOH) are vital to prevent potent vision loss and ensure the safety and effectiveness of dexamethasone (DEX) injections. The study aimed to develop a novel nomogram for predicting the risk of SIOH and determining safety zones for steroid injections. Methods: This single-center, retrospective, case-control study included a total of 154 eyes with available measured axial length that had undergone AS-OCT and DEX implantation at the Yonsei University Health System. The eyes were categorized into the SIOH (n = 39) and post-steroid normal IOP (n = 115) groups. We measured intraocular pressure (IOP) for all eyes prior to DEX implantation, at 1 week post-implantation, and at 1, 2, 3, 6, and 12 months thereafter. We used AS-OCT to analyze the trabecular meshwork (TM) height and ocular parameters. Results: The predictive nomogram, including TM height, yielded an AUC of 0.807 (95 % confidence interval [CI], 0.737-0.877) and demonstrated significantly higher predictive accuracy than that of previous nomograms, which did not consider TM height and had an AUC of 0.644 (95 % CI, 0.543-0.745) (p = 0.031). The calibration plot demonstrated a strong predictive accuracy for a predicted value of approximately 0.4. We established cutoff values to ensure different levels of sensitivity and specificity within the safety zone following DEX implantation. Conclusion: Our improved nomogram incorporating TM height as a newly identified risk factor, established a safety threshold for intravitreal DEX implantation, helping identify safe individuals from those who require caution.

Clinical characteristics of open-angle glaucoma progression with peripapillary microvasculature dropout in different locations.

OBJECTIVE: The study attempted to identify clinical characteristics associated with structural progression in open-angle glaucoma (OAG) in the presence of MvD in different locations. METHODS: A total of 181 consecutive OAG eyes (follow-up 7.3 ± 4.0 years), which demonstrated peripapillary choroidal MvD (defined as a focal capillary loss with no visible microvascular network in choroidal layer) on optical coherence tomography (OCT) angiography (OCTA), were divided based on the location of MvD. Structural progression was determined using trend-based analysis of the Guided Progression Analysis software of Cirrus OCT. RESULTS: MvD was identified in the temporal quadrant in 110 eyes (temporal MvD; 60.5 ± 12.6 years), and in the inferior quadrant in 71 eyes (inferior MvD; 60.3 ± 11.1 years). After adjusting for age, average intraocular pressure (IOP) and baseline retinal nerve fibre layer (RNFL) thickness and visual field mean deviation, inferior MvD eyes showed faster rates of thinning in the inferior RNFL (mean (95% CI); -0.833 (-1.298 to -0.367)) compared to temporal MvD eyes (-0.144 (-0.496 to 0.207)) when long-term IOP fluctuation was larger than the median value (1.7 mmHg; P = 0.022). Long-term IOP fluctuations were independently associated with inferior RNFL thinning in eyes with inferior MvD (P = 0.002) but not in eyes with temporal MvD. CONCLUSIONS: In OAG eyes, the rates of RNFL and GCIPL thinning were comparable regardless of MvD locations. However, inferior MvD is associated with faster RNFL and GCIPL thinning in the same quadrant when long-term IOP fluctuation is present. Structural progression in the presence of temporal MvD was less associated with IOP fluctuation.

Optic Nerve Head Morphology is Associated with the Initial Location of Structural Progression in Early Open Angle Glaucoma.

PRCIS: Glaucoma eyes with a small cup-to-disk ratio (CDR) tend to show retinal nerve fiber layer progression earlier than ganglion cell-inner plexiform layer progression. PURPOSE: To investigate the effects of clinical variables on the temporal relationship between macular ganglion cell-inner plexiform layer (mGCIPL) loss and peripapillary retinal nerve fiber layer (pRNFL) loss in glaucoma. METHODS: This retrospective observational study used medical records of patients diagnosed with open angle glaucoma. Structural change was determined using guided progression analysis software of Cirrus optical coherence tomography. Based on the time of detection of pRNFL and mGCIPL changes, eyes showing progressive layer loss were categorized into the pRNFL-first and mGCIPL-first groups. The association between sites of layer thinning and clinical variables such as major retinal arterial angles and several optic disk measurements, including disk area, average CDR, and vertical CDR, were analyzed. RESULTS: A total of 282 eyes were included in the study, of which 104 showed structural progression either in the mGCIPL or pRNFL. Out of these, 49 eyes showed the first progression in pRNFL, while 37 eyes showed the first progression in mGCIPL. The minimum mGCIPL thickness, pRNFL thickness, average CDR, vertical CDR, and location of progression were significantly different between the 2 groups ( P =0.041, P =0.034, P =0.015, P <0.001, and P <0.001, respectively). In multivariate analysis, average CDR and vertical CDR were significantly associated with the progression site ( P =0.033 and P =0.006, respectively). The structural changes in the inferoinferior area and the superior vulnerability zone were significantly associated with RNFL-first progression ( P <0.001 for both). CONCLUSION: The location of layer loss and CDR are related to the layer where loss is first detected (either pRNFL or mGCIPL) in open angle glaucoma.

Alterations of Macular Structure in Non-Glaucomatous Subjects With Obstructive Pulmonary Function.

Purpose: The purpose of this study was to identify possible associations between obstructive pulmonary function and macular structure parameters on optical coherence tomography (OCT) and angiography in subjects without glaucomatous optic neuropathy. Methods: A total of 70 patients were prospectively enrolled from June to December 2021 as a part of All About Life Yongin-Pulmonary/Psychiatry, Rehabilitation, Eye (AALY PRE) cohort in Yongin Severance Hospital. Patients underwent intraocular pressure (IOP), visual acuity measurements, cirrus OCT, OCT angiography, and pulmonary function testing (PFT) on the same day. Subjects with glaucomatous optic nerve damage were excluded. Those whose first second of forced expiration (FEV1) to forced vital capacity (FVC) ratio was below 70% were diagnosed with obstructive pulmonary function. Vessel densities (VDs) of retinal superficial vascular plexus were compared. Results: Patients with obstructive function (n = 30) were significantly older than those with normal pulmonary function (n = 40, P < 0.001). After adjusting for age, IOP, and average ganglion cell-inner plexiform layer (GCIPL) thickness, macular VD was significantly decreased in all sectors except for the nasal sector in subjects with obstructive pulmonary function in comparison to those with normal function (P = 0.006). Multivariate regression analysis demonstrated that macular VD was linearly associated with FEV1/FVC (ß = 0.102, P = 0.031). In subjects with obstructive function, the severity of pulmonary obstruction, FEV1, was linearly associated with GCIPLT (ß = 0.302, P = 0.017). Conclusions: Obstructive pulmonary function is associated with reduced macular VD in subjects without glaucoma. Among subjects with obstructive pulmonary function, the severity of pulmonary obstruction is associated with GCIPL thickness in the macular region. Further studies are needed on the relationship between pulmonary function and macular disease.

Effect of antihypertensive medications on the risk of open-angle glaucoma.

The purpose of this study was to identify the effect of antihypertensive medication on risks of open-angle glaucoma (OAG) among patients diagnosed with hypertension (HTN). A total of 5,195 patients, who were diagnosed with HTN between January 1, 2006 and December 31, 2015, and subsequently diagnosed with OAG, were selected for analysis. For each OAG patient, 5 non-glaucomatous, hypertensive controls were matched (n = 25,975) in hypertension diagnosis date, residential area, insurance type and economic status. Antihypertensive medications were stratified into 5 types: angiotensin converting enzyme inhibitor (ACEi), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), ß-blockers and diuretics. Relative risks were calculated. After adjusting for age, sex, body mass index, lifestyle, comorbidities, blood pressure (BP), follow-up duration, and use of other types of antihypertensive drugs, ARB and CCB were found to slightly increase OAG risks (RR 1.1087 (95% CI 1.0293-1.1942); 1.0694 (1.0077-1.1349), respectively). Combinations of ARB with diuretics (1.0893 (1.0349-1.1466)) and CCB (1.0548 (1.0122-1.0991)) also increased OAG risks. The risks for OAG were found to increase by antihypertensive medication use, but the effects appeared to be small. Further studies are necessary to identify the associations of increased BP, medication and therapeutic effect with OAG.

Peripapillary choroidal microvasculature dropout is associated with poor prognosis in optic neuritis.

PURPOSE: To identify peripapillary choroidal microvasculature dropout (MvD) in eyes with optic neuritis and its association with longitudinal changes in retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIP) thicknesses following diagnosis. METHODS: A total of 48 eyes with optic neuritis was evaluated to identify the presence of peripapillary choroidal MvD, defined as a focal capillary loss with no visible microvascular network in choroidal layer, using optical coherence tomography (OCT) angiography (OCTA). Patients were divided based on the presence of MvD. OCT and standard automated perimetry (SAP) conducted at 1, 3 and 6 months follow-up were analyzed. RESULTS: MvD was identified in 20 of 48 eyes (41.7%) with optic neuritis. MvD was most commonly found in the temporal quadrant (85.0%), and peripapillary retinal vessel density in the temporal quadrant was significantly lower in eyes with MvD (P = 0.012). At 6 months follow-up, optic neuritis eyes with MvD showed significantly thinner GCIP in superior, superotemporal, inferior and inferotemporal sectors (P<0.05). No significant difference was noted in SAP parameters. The presence of MvD was significantly associated with thinner global GCIP thickness at 6 months follow-up (OR 0.909, 95% CI 0.833-0.992, P = 0.032). CONCLUSION: Optic neuritis showed peripapillary choroidal microvascular impairment in the form of MvD. MvD was associated with structural deterioration at macular GCIP. Further studies are necessary to identify the causal relationship between microvascular impairment and retinal nerve fiber layer damage in optic neuritis.

Effect of Intraoperative Mitomycin C on the Surgical Outcomes of Ahmed Glaucoma Valve Implantation with Ciliary Sulcus Tube Placement.

PURPOSE: To evaluate the effect of intraoperative mitomycin C (MMC) on the surgical outcomes of ciliary sulcus (CS) Ahmed glaucoma valve (AGV) tube placement. METHODS: A retrospective review of medical records of 54 consecutive patients who underwent AGV implantation with tube placed in CS was performed. Consecutive cases operated without the use of intraoperative MMC from 2017 to 2019 were compared with consecutive cases operated with MMC from 2019 to 2021. Surgical failure was defined as intraocular pressure (IOP) exceeding 21 mmHg in two consecutive visits after postoperative 3 months or ≤30% IOP reduction, IOP ≤5 mmHg in two consecutive visits, or loss of light perception. Kaplan-Meier survival analysis and log-rank test were performed to compare the surgical failure rates. RESULTS: A total of 54 eyes of 54 patients were investigated. Mean follow-up period after AGV implantation was 1.4 ± 0.8 years. The MMC group showed significantly lower IOP during the 1st postoperative month (20.5 ± 8.6 mmHg vs. 15.8 ± 6.4 mmHg, p = 0.027), but the difference did not persist 6 months after the surgery (p = 0.805). The mean number of postoperative antiglaucoma medications was significantly lower in the MMC group in the 1st postoperative month (p = 0.047) but no difference was found at 6 months. No statistical difference was noted in the rates of postoperative complications. Kaplan-Meier survival analysis showed comparable survival rates between MMC group and no MMC group (p = 0.356). CONCLUSIONS: The intraoperative use of MMC significantly lowered IOP in the 1st postoperative month but did not increase 6 months success rates in patients receiving AGV tube placement in CS.

Association of trabecular meshwork height with steroid-induced ocular hypertension.

It is important to identify at-risk patients prior to administering steroid injections to prevent avoidable irreversible blindness inducted by steroid-induced ocular hypertension (SIOH). We aimed to investigate the association of SIOH following intravitreal dexamethasone implantation (OZURDEX) using anterior segment optical coherence tomography (AS-OCT). We conducted a retrospective case control study to assess the association between trabecular meshwork and SIOH. A total of 102 eyes that underwent both AS-OCT and intravitreal dexamethasone implant injection were divided into the post-steroid ocular hypertension and normal intraocular pressure groups. Ocular parameters that can contribute to intraocular pressure were measured using AS-OCT. Univariable logistic regression analysis was used to calculate the odds ratio of the SIOH and significant variables were further analyzed using a multivariable model. Trabecular meshwork (TM) height was significantly shorter in the ocular hypertension group (716.13 ± 80.55 µm) than that in the normal intraocular pressure group (784.27 ± 82.33 µm) (p < 0.001). The receiver operating characteristic curve technique analysis showed that the optimal cut-off of ≥ 802.13 µm for TM height specificity was 96.2%, and TM height with < 646.75 µm had a sensitivity of 94.70%. The odds ratio of the association was 0.990 (p = 0.001). TM height was identified as a newly observed association with SIOH. TM height can be assessed using AS-OCT, with acceptable sensitivity and specificity. Caution must be exercised while injecting steroids in patients with short TM height (especially < 646.75 µm) as it may cause SIOH and irreversible blindness.

Increased Risks of Open-Angle Glaucoma in Untreated Hypertension.

PURPOSE: Hypertension (HTN) has been associated with open-angle glaucoma (OAG), but whether elevated blood pressure (BP) alone is associated with OAG is unknown. Whether stage 1 hypertension, as per the 2017 American College of Cardiology/American Heart Association (ACC/AHA) BP guidelines, increases the risk of the disease is uncertain. DESIGN: Retrospective, observational, cohort study. METHODS: A total of 360,330 subjects who were ≥40 years of age and not taking antihypertensive or antiglaucoma drugs at the time of health examinations between January 1, 2002, and December 31, 2003, were included. Subjects were categorized based on their untreated BP, into normal BP (systolic BP [SBP] <120 and diastolic BP [DBP] <80 mm Hg; n = 104,304), elevated BP (SBP 120-129 and DBP <80 mm Hg; n = 33,139), stage 1 HTN (SBP 130-139 or DBP 80-89 mm Hg; n = 122,534), or stage 2 HTN (SBP ≥140 or DBP ≥90mm Hg; n = 100,353). Cox regression analysis was performed to calculate hazard ratios (HR) of OAG risk. RESULTS: The mean age of the subjects was 51.17 ± 8.97 years, and 56.2% were male. During a mean follow-up period of 11.76 ± 1.37 years, 12,841 subjects (3.56%) were diagnosed with OAG. Multivariable-adjusted HRs (95% CIs) were 1.056 (0.985-1.132) for elevated BP, 1.101(1.050-1.155) for stage 1 HTN, and 1.114(1.060-1.170) for stage 2 HTN with normal BP as the reference. CONCLUSIONS: The risk for OAG becomes greater with increases in untreated BP. Stage 1 HTN per the 2017 ACC/AHA BP guidelines is a significant risk factor for OAG.

Ciliary Neurotrophic Factor Derived From Astrocytes Protects Retinal Ganglion Cells Through PI3K/AKT, JAK/STAT, and MAPK/ERK Pathways.

Purpose: The purpose of this study was to investigate the roles of ciliary neurotrophic factor (CNTF) on the protective effects of astrocytes on retinal ganglion cells (RGCs). Methods: Primary RGCs were isolated from neonatal rats. Oxidative stress was induced, and the effects of co-culture with astrocytes and CNTF treatment on RGCs were evaluated. The pathways commonly altered by astrocytes and CNTF were investigated. Effects of each pathway were investigated using pathway inhibitors against PI3K/AKT, JAK/STAT, and MAPK/ERK. RNA sequencing was performed to identify the genes upregulated and downregulated by CNTF treatment. Results: Astrocytes improved the viability and increased ß3-tubulin expression in RGCs. The concentration of CNTF increased in the RGC-astrocyte co-culture medium. The protective effects of astrocytes were abolished by neutralization with the anti-CNTF antibody; thus, CNTF may play an important role in the effects mediated by astrocytes. Furthermore, CNTF treatment alone enhanced the viability and ß3-tubulin expression of RGCs and increased the population of viable RGCs under oxidative stress. The PI3K/AKT pathway was associated with both RGC viability and ß3-tubulin expression. However, the JAK/STAT pathway increased the viability of RGCs, whereas the MAPK/ERK pathway was associated with ß3-tubulin expression. RNA sequencing revealed the CNTF-upregulated genes associated with response to DNA damage and downregulated genes associated with photoreceptor cell differentiation. Conclusions: Our data revealed protective effects of astrocyte-derived CNTF on RGCs. In addition, we showed that multiple pathways exert these protective effects and identified the novel genes involved. These results may be helpful in developing treatments for RGC injury.

Systemic Arterial Stiffness Is Associated With Structural Progression in Early Open-Angle Glaucoma.

Purpose: The purpose was to identify association between systemic arterial stiffness predicted by brachial-ankle pulse wave velocity (PWV) and initial location of structural progression in early open-angle glaucoma. Methods: Patients with early open-angle glaucoma who underwent PWV measurements were subjected to a retrospective review of medical records. A total of 160 eyes of 160 patients were subjected to analyses. Patients were categorized into three PWV groups. Structural progression was determined using event-based analysis of the Guided Progression Analysis software of Cirrus optical coherence tomography. Results: Thirty-eight patients had a PWV of 1400 cm/s or less on both the left and right sides (low PWV, 39.5% females, 53.9 ± 8.8 years old), and 46 patients showed a PWV of 1800 cm/s or more on either side (high PWV; 54.3% females, 71.3 ± 5.8 years old). The rest of the patients had an intermediate PWV (n = 76, 50.0% females, 59.8 ± 8.6 years old). Among patients who showed progression in 69.3 ± 41.5 months, macular ganglion cell-inner plexiform layer (mGCIPL) loss preceded peripapillary retinal nerve fiber layer (ppRNFL) loss in 86.7% of high PWV group (n = 15, 60.0% females, 70.0 ± 6.0 years old) in comparison with 26.7% of the low PWV group (P = 0.002). The PWV was significantly higher in patients whose structural progression was first observed at mGCIPL (1744.1 ± 347.7 cm/s) than patients whose initial location was ppRNFL (1452.0 ± 201.0 cm/s; P = 0.012). A high PWV was associated with increased likelihood of structural progression at mGCIPL (odds ratio, 7.484; 95% confidence interval, 1.212-49.196; P = 0.030) among patients who showed progression. Conclusions: PWV is a significant predictor of the location of structural progression in open-angle glaucoma. Vascular insufficiency may be an important aspect in the pathogenesis of glaucoma.

What Are the Factors Associated with the Structural Damage Differences in Open-Angle Glaucoma? RNFL- and GCIPL-Dominant Progression.

We sought to analyze the parameters associated with retinal nerve fiber layer (RNFL)-dominant progression or ganglion cell-inner plexiform layer (GCIPL)-dominant progression in patients with open-angle glaucoma. A prospective observational study was conducted. Overall, 58 eyes from 33 patients with open-angle glaucoma were categorized into the following two groups: patients with RNFL- and GCIPL-dominant progression, and the primary outcome was the difference in associated factors between two groups. Higher pre-treatment and mean IOP, greater lamina cribrosa curvature index (LCCI), and younger age were more significantly associated with the RNFL-dominant progression group than the GCIPL-dominant progression group. When adjusting for mean IOP, age, LCCI, and microvascular dropout (MVD), only pre-treatment IOP was significantly associated with the RNFL-dominant progression group. However, when adjusting for pre-treatment IOP, age, LCCI, and MVD, both higher mean IOP and greater LCCI were significantly associated with RNFL-dominant progression. In conclusion, pre-treatment and mean IOP and LCCI were more strongly associated with the RNFL-dominant progression group than the GCIPL-dominant progression group. In contrast, age, peripapillary choroidal microvascular dropout, and systolic and diastolic blood pressures tended to damage the GCIPL predominantly rather than the RNFL. Therefore, our findings suggest the potential to set different treatment targets and identify various treatment methods for each group.