Identifying new drugs and targets to treat rapidly elevated intraocular pressure for angle closure and secondary glaucomas to curb visual impairment and prevent blindness.

A multitude of pharmacological compounds have been shown to lower and control intraocular pressure (IOP) in numerous species of animals and human subjects after topical ocular dosing or via other routes of administration. Most researchers have been interested in finding drug candidates that exhibit a relatively long duration of action from a chronic therapeutic use perspective, for example to treat ocular hypertension (OHT), primary open-angle glaucoma and even normotensive glaucoma. However, it is equally important to seek and characterize treatment modalities which offer a rapid onset of action to help provide fast relief from quickly rising IOP that occurs in certain eye diseases. These include acute angle-closure glaucoma, primary angle-closure glaucoma, uveitic and inflammatory glaucoma, medication-induced OHT, and other secondary glaucomas induced by eye injury or infection which can cause partial or complete loss of eyesight. Such fast-acting agents can delay or prevent the need for ocular surgery which is often used to lower the dangerously raised IOP. This research survey was therefore directed at identifying agents from the literature that demonstrated ocular hypotensive activity, normalizing and unifying the data, determining their onset of action and rank ordering them on the basis of rapidity of action starting within 30-60 min and lasting up to at least 3-4 h post topical ocular dosing in different animal species. This research revealed a few health authority-approved drugs and some investigational compounds that appear to meet the necessary criteria of fast onset of action coupled with significant efficacy to reduce elevated IOP (by ≥ 20%, preferably by >30%). However, translation of the novel animal-based findings to the human conditions remains to be demonstrated but represent viable targets, especially EP2-receptor agonists (e.g. omidenepag isopropyl; AL-6598; butaprost), mixed activity serotonin/dopamine receptor agonists (e.g. cabergoline), rho kinase inhibitors (e.g. AMA0076, Y39983), CACNA2D1-gene product inhibitors (e.g. pregabalin), melatonin receptor agonists, and certain K+-channel openers (e.g. nicorandil, pinacidil). Other drug candidates and targets were also identified and will be discussed.

Evaluation of the effects of duloxetine treatment on anterior segment parameters by optical coherence tomography.

PURPOSE: To evaluate the effects of Duloxetine on anterior segment parameters and intraocular pressure (IOP) in open angle eyes. METHODS: 38 eyes of 38 patients with fibromyalgia who had open or wide open angles according to the Shaffer classification. Anterior segment optic coherence tomography was performed before and after (month 3) Duloxetine treatment. IOP, central corneal thickness (CCT), corneal endothelial cell density (CECD) and anterior chamber depth (ACD) were also recorded and evaluated. RESULTS: No statistically significant difference was determined in IOP, CCT and CECD (p > 0.05). However, a statistically significant decrease was determined in both the temporal and nasal anterior chamber angle, angle opening distance, nasal trabecular-iris space area and ACD values between the baseline and month 3 (p < 0.001). DISCUSSION: We think that the short term use of Duloxetine does not lead to clinically significant changes despite their statistically significant effects on the anterior chamber parameters.

Acute angle closure glaucoma precipitated by homeopathic eyedrops containing Atropa belladonna.

Acute angle closure glaucoma is a sight-threatening condition that may lead to blindness. This is a case report of a woman who presented to the emergency department (ED) with acute angle closure glaucoma following use of an over-the-counter (OTC) homeopathic eye drop containing atropa belladonna (deadly nightshade). A 55-year-old woman presented to the ED with a 5-day history of left eye redness, swelling, tearing, and foreign-body sensation that had acutely worsened in the last two days. Her exam revealed mild left conjunctival injection with watery tearing and a hazy appearance of her left cornea. Fluorescein staining was negative, while tonometry revealed elevated intraocular pressure on the left, suggestive of acute angle closure glaucoma. She was urgently referred to ophthalmology. The etiology of the acute angle closure glaucoma was initially unclear however, with additional prompting, she revealed that two days prior she had started using homeopathic OTC eye drops. Inspection of the eyedrop's ingredients revealed that atropa belladonna was the primary ingredient and likely precipitated her isolated episode of acute angle closure glaucoma. A high level of clinical suspicion and focused ophthalmic exam including tonometry is essential to identify acute angle closure glaucoma in the ED. We present a case report of acute angle closure glaucoma associated with the use of homeopathic belladonna-containing eyedrops. Our report reinforces the necessity to perform thorough medication and supplement history given the prevalence of physiologically active substances available in OTC medications.

Lens extraction for chronic angle-closure glaucoma.

BACKGROUND: Primary angle-closure glaucoma (PACG) is characterized by a rise in intraocular pressure (IOP) secondary to aqueous outflow obstruction, with relative pupillary block being the most common underlying mechanism. There is increasing evidence that lens extraction may relieve pupillary block and thereby improve IOP control. As such, comparing the effectiveness of lens extraction against other commonly used treatment modalities can help inform the decision-making process. OBJECTIVES: To assess the effectiveness of lens extraction compared with other interventions in the treatment of chronic PACG in people without previous acute angle-closure attacks. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, one other database, and two trials registers (December 2019). We also screened the reference lists of included studies and the Science Citation Index database. We had no date or language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) comparing lens extraction with other treatment modalities for chronic PACG. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. MAIN RESULTS: We identified eight RCTs with 914 eyes. We obtained data for participants meeting our inclusion criteria for these studies (PACG only, no previous acute angle-closure attacks), resulting in 513 eyes included in this review. The participants were recruited from a diverse range of countries. We were unable to conduct meta-analyses due to different follow-up periods and insufficient data. One study compared phacoemulsification with laser peripheral iridotomy (LPI) as standard care. Participants in the phacoemulsification group were less likely to experience progression of visual field loss (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.13 to 0.91; 216 eyes; moderate certainty evidence), and required fewer IOP-lowering medications (mean difference [MD] -0.70, 95% CI -0.89 to -0.51; 263 eyes; moderate certainty evidence) compared with standard care at 12 months. Moderate certainty evidence also suggested that phacoemulsification improved gonioscopic findings at 12 months or later (MD -84.93, 95% CI -131.25 to -38.61; 106 eyes). There was little to no difference in health-related quality of life measures (MD 0.04, 95% CI -0.16 to 0.24; 254 eyes; moderate certainty evidence), and visual acuity (VA) (MD 2.03 ETDRS letter, 95% CI -0.77 to 4.84; 242 eyes) at 12 months, and no observable difference in mean IOP (MD -0.03mmHg, 95% CI -2.34 to 2.32; 257 eyes; moderate certainty evidence) compared to standard care. Irreversible loss of vision was observed in one participant in the phacoemulsification group, and three participants in standard care at 36 months (moderate-certainty evidence). One study (91 eyes) compared phacoemulsification with phaco-viscogonioplasty (phaco-VGP). Low-certainty evidence suggested that fewer IOP-lowering medications were needed at 12 months with phacoemulsification (MD -0.30, 95% CI -0.55 to -0.05). Low-certainty evidence also suggested that phacoemulsification may have improved gonioscopic findings at 12 months or later compared to phaco-VGP (angle grading MD -0.60, 95% CI -0.91 to -0.29; TISA500 MD -0.03, 95% CI -0.06 to -0.01; TISA750 MD -0.03, 95% CI -0.06 to -0.01; 91 eyes). Phacoemulsification may result in little to no difference in best corrected VA at 12 months (MD -0.01 log MAR units, 95% CI -0.10 to 0.08; low certainty evidence), and the evidence is very uncertain about its effect on IOP at 12 months (MD 0.50 mmHg, 95% CI -2.64 to 3.64; very low certainty evidence). Postoperative fibrin reaction was observed in two participants in the phacoemulsification group and four in the phaco-VGP group. Three participants in the phaco-VGP group experienced hyphema. No data were available for progression of visual field loss and quality of life measurements at 12 months. Two studies compared phacoemulsification with phaco-goniosynechialysis (phaco-GSL). Low-certainty evidence suggested that there may be little to no difference in mean IOP at 12 months (MD -0.12 mmHg, 95% CI -4.72 to 4.48; 1 study, 32 eyes) between the interventions. Phacoemulsification did not reduce the number of IOP-lowering medications compared to phaco-GSL at 12 months (MD -0.38, 95% CI -1.23 to 0.47; 1 study, 32 eyes; moderate certainty evidence). Three eyes in the phaco-GSL group developed hyphemas. No data were available at 12 months for progression of visual field loss, gonioscopic findings, visual acuity, and quality of life measures. Three studies compared phacoemulsification with combined phaco-trabeculectomy, but the data were only available for one study (63 eyes). In this study, low-certainty evidence suggested that there was little to no difference between groups in mean change in IOP from baseline (MD -0.60 mmHg, 95% CI -1.99 to 0.79), number of IOP-lowering medications at 12 months (MD 0.00, 95% CI -0.42 to 0.42), and VA measured by the Snellen chart (MD -0.03, 95% CI -0.18 to 0.12). Participants in the phacoemulsification group had fewer complications (risk ratio [RR] 0.59, 95% CI 0.34 to 1.04), and the phaco-trabeculectomy group required more IOP-lowering procedures (RR 5.81, 95% CI 1.41 to 23.88), but the evidence was very uncertain. No data were available for other outcomes. AUTHORS' CONCLUSIONS: Moderate certainty evidence showed that lens extraction has an advantage over LPI in treating chronic PACG with clear crystalline lenses over three years of follow-up; ultimately, the decision for intervention should be part of a shared decision-making process between the clinician and the patient. For people with chronic PACG and visually significant cataracts, low certainty evidence suggested that combining phacoemulsification with either viscogonioplasty or goniosynechialysis does not confer any additional benefit over phacoemulsification alone. There was insufficient evidence to draw any meaningful conclusions regarding phacoemulsification versus trabeculectomy. Low certainty evidence suggested that combining phacoemulsification with trabeculectomy does not confer any additional benefit over phacoemulsification alone, and may cause more complications instead. These conclusions only apply to short- to medium-term outcomes; studies with longer follow-up periods can help assess whether these effects persist in the long term.

Laser peripheral iridoplasty for chronic angle closure.

BACKGROUND: In at least a third of primary angle closure cases, appositional angle closure persists after laser peripheral iridotomy, and further intervention may be considered. Laser peripheral iridoplasty (LPIp) can be used in treating chronic angle closure when angle closure persists after laser peripheral iridotomy. Previous reviews have found insufficient data to determine its clinical effectiveness, compared to other interventions. This is an update of a Cochrane Review first published in 2008 and updated in 2012. It examines all studies to date to establish whether LPIp shows any effectiveness over other available treatment options. OBJECTIVES: To assess the effectiveness of laser peripheral iridoplasty in the treatment of people with chronic angle closure, when compared to laser peripheral iridotomy, medical therapy or no further treatment. SEARCH METHODS: We searched various electronic databases. The date of the search was 20 December 2020. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) assessing the use of LPIp in cases of suspected primary angle closure (PACS), confirmed primary angle closure (PAC), or primary chronic angle-closure glaucoma (PACG). We applied no restrictions with respect to gender, age or ethnicity of participants. Trials evaluating LPIp for acute attacks of angle closure were not eligible. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Two authors independently assessed studies for risk of bias using Cochrane's 'risk of bias' tool. We collected adverse effects information from the trials. MAIN RESULTS: We included four RCTs involving 252 participants (276 eyes). In total, three different methods of intervention were used and 15 outcomes reported, with different time points. We used narrative synthesis to describe the majority of the findings, as meta-analysis was only possible for a limited number of outcomes due to the variation in study design and outcomes assessed. Study Characteristics Participants were adults recruited from outpatient settings in the UK, Singapore, China and Korea with either PACS, PAC or PACG. All studies compared argon LPIp (as either a primary or secondary procedure) to an alternative intervention or no further treatment. Three studies were of parallel group design, and one within-person, randomised by eye. All studies showed elements of high risk of bias. Due to the nature of the intervention assessed, a lack of masking of both participants and assessors was noted in all trials. Findings Laser peripheral iridoplasty with iridotomy versus iridotomy alone as a primary procedure Two RCTs assessed the use of argon LPIp as a primary procedure with peripheral iridotomy, compared with peripheral iridotomy alone. However, neither study reported data for the primary outcome, disease progression. Argon LPIp showed no evidence of effect on: final mean intraocular pressure (IOP) at 3 months and 12 months (mean difference (MD) 0.39 mmHg, 95% confidence interval (CI) -1.07 to 1.85; I2 = 38%; 2 studies, 174 participants; low-certainty evidence); further surgical or laser intervention at 12 months (risk ratio (RR) 1.21, 95% CI 0.66 to 2.21; 1 study, 126 participants; low-certainty evidence); or mean number of additional medications required at 12 months (MD 0.10, 95% CI -0.34 to 0.54; 1 study, 126 participants; low-certainty evidence). Complications were assessed at 3 to 12 months (2 studies, 206 participants; low-certainty evidence) and found to be mild and uncommon, with comparable levels between groups. The only severe complication encountered was one case of malignant glaucoma in one study's argon LPIp group. Quality of life measures were not assessed. In the other study, investigators found that argon LPIp showed no evidence of effect on final mean anterior segment optical coherence tomography (AS-OCT) measurements, including anterior chamber depth (MD 0.00 mm, 95% CI -0.10 to 0.10; 24 participants, 48 eyes; very low-certainty evidence). Laser peripheral iridoplasty as a secondary procedure versus no treatment One RCT assessed the use of argon LPIp as a secondary procedure compared with no further treatment in 22 participants over three months. Disease progression, additional medications required, complications, further surgical or laser intervention, and quality of life outcomes were not assessed. There was only very low-certainty evidence regarding final maximum IOP value (MD -1.81 mmHg, 95% CI -3.11 to -0.51; very low-certainty evidence), with no evidence of effect on final minimum IOP values (MD -0.31 mmHg, 95% CI -1.93 to 1.31; very low-certainty evidence). The evidence is very uncertain about the effect of argon LPIp on AS-OCT parameters. The trial did not report AS-OCT measurements for the control group. Laser peripheral iridoplasty as a secondary procedure versus medication One RCT assessed the use of argon LPIp as a secondary procedure compared with travoprost 0.004% in 80 participants over 12 months. The primary outcome of disease progression was reported for this method: argon LPIp showed no evidence of effect on mean final cup/disk ratio (MD -0.03, 95% CI -0.11 to 0.05; low-certainty evidence). Argon LPIp showed no evidence of effect for: mean change in IOP (MD -1.20 mmHg, 95% CI -2.87 to 0.47; low-certainty evidence) or mean number of additional medications (MD 0.42, 95% CI 0.23 to 0.61; low-certainty evidence). Further surgical intervention was required by one participant in the intervention group alone, with none in the control group  (low-certainty evidence). No serious adverse events were reported, with mild complications consisting of two cases of 'post-laser IOP spike' in the argon LPIp group. Quality of life measures were not assessed. The evidence is very uncertain about the effect of argon LPIp on AS-OCT parameters. The trial did not report AS-OCT measurements for the control group. Adverse events Availability of data were limited for adverse effects. Similar rates were observed in control and intervention groups, where reported. Serious adverse events were rare. AUTHORS' CONCLUSIONS: After reviewing the outcomes of four RCTs, argon LPIp as an intervention may be no more clinically effective than comparators in the management of people with chronic angle closure. Despite a potential positive impact on anterior chamber morphology, its use in clinical practice in treating people with chronic angle closure is not supported by the results of trials published to date. Given these results, further research into LPIp is unlikely to be worthwhile.

Outcomes of primary trabeculectomy with mitomycin-C for primary angle closure glaucoma among supervised trainees in a tertiary eye center in Manila.

PURPOSE: To evaluate efficacy and safety of trabeculectomy with mitomycin C (trab-MMC) for primary angle closure glaucoma (PACG) performed by ophthalmology trainees. METHODS: This was a six-year retrospective study of patients with primary trab-MMC with PACG performed by ophthalmology trainees in a tertiary urban eye center. Outcomes included intraocular pressure (IOP), number of medications, and complications. RESULTS: There were 120 PACG eyes that underwent trab-MMC performed by trainees. The mean follow-up duration was 28.6 ± 20.8 months. At 24 months, postoperative IOP decreased from 32.1 ± 12.0 mm Hg to 14.8 ± 6.9 mm Hg (p<0.0001) with decrease in glaucoma medications [0 (0), 0-2; p<0.0001]. Half of surgeries, 64/120 (53.8%) utilized MMC-onlay and the other half, 55/120(46.2%) received MMC sub-tenon injection. Half 60/120 (50.4%) utilized releasable sutures. Majority 55/120 (46.2%) utilized conjunctival closure near the corneal limbus while 34/120 (28.6%) used a conjunctival skirt. Cumulative complete surgical success rates were 63.3%, 55.83%, and 42.5% at 6, 12, and 24 months, respectively. Most complications were minor, including high IOP (25.0%), bleb leaks (13.3%), and cystic blebs (15.0%). Bleb needling was the most common (24.2%) post-op surgical intervention. CONCLUSION: Among supervised ophthalmology trainees in the Philippines, trab-MMC for PACG was effective in lowering IOP long term and decreasing glaucoma medications, and surgical success rates were generally comparable with trainee studies from first world nations. Complications were minor and not sight threatening.

Peroxynitrite is a novel risk factor and treatment target of glaucoma.

To investigate the association between systemic nitrotyrosine (NT) levels and primary angle-closure glaucoma (PACG) and primary open-angle glaucoma (POAG) and the mechanism involved. A case control study was conducted in the Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Fudan University from April 2017 to December 2017. A total of 400 participants were consecutively recruited into this study (100 PACG, 100 POAG and 200 controls). Multivariable logistic regression analysis was performed to identify the association between serum NT level and PACG or POAG. Clinical results were validated in cell and animal models. Among 200 glaucoma patients, 101 (50.5%) were women; the age was 57.07 ± 14.51 years. 106 (53%) control participants were women and age was 58.34 ± 14.04 years. Serum levels of NT in PACG and POAG patients are significantly higher than controls (1808.53 ± 417.76 nmol/L vs. 1270.62 ± 454.60 nmol/L, p < 0.001; 1718.63 ± 437.29 nmol/L vs. 1258.38 ± 460.72 nmol/L, p < 0.001). Further, elevated serum NT level increases the risk of developing PACG (OR = 1.003, 95% CI: 1.002 to 1.004, p < 0.001) and POAG (OR = 1.002, 95% CI: 1.002 to 1.003, p < 0.001). Consistent with the clinical data, serum and aqueous humour NT levels are significantly higher in caveolin 1 knockout (Cav1 KO) mice, an animal model of glaucoma. More importantly, peroxynitrite (PN) scavenger MnTMPyP and its transduction molecule PARP inhibitor significantly reduce intraocular pressure in Cav1 KO mice. Our data show for the first time that NT is a systemic risk factor and local treatment target of glaucoma.

Potentially inappropriate prescriptions of anticholinergic medications in patients with closed-angle glaucoma.

PURPOSE: Glaucoma is the leading cause for blindness after cataracts worldwide. The aim was to identify anticholinergic drugs prescribed to patients diagnosed with closed-angle glaucoma in Colombia. METHODS: This cross-sectional study identified the prescribing patterns of cholinergic antagonists related to the increased intraocular pressure in patients diagnosed with closed-angle glaucoma from a Colombian database. The Anticholinergic Drug Scale was used to quantify the anticholinergic burden. RESULTS: We identified 1958 patients with closed-angle glaucoma, with a mean age of 70.5 ± 10.3 years, 72.9% of whom were women. Cholinergic antagonists were prescribed in at least 32.4% of cases. An age range between 75 and 84 years (odds ratio (OR) 2.35, 95% confidence interval (CI) 1.366-4.059) and being aged 85 years or older (OR 3.40, 95% CI 1.809-6.425) were associated with a greater probability of receiving an anticholinergic burden between 1 and 2 points. Females (OR 1.54, 95% CI 1.096-2.181) had a higher probability of receiving an anticholinergic burden ≥ 3 points. Interactions between antiglaucoma medications and anticholinergic treatments were identified in 32.1% of the patients. CONCLUSIONS: Most patients were prescribed multiple antiglaucoma medications, reflecting a large number of potentially inappropriate prescriptions, with anticholinergic drugs, related to the increased intraocular pressure.

INTRAOCULAR PRESSURE CHANGES AFTER DEXAMETHASONE IMPLANT IN PATIENTS WITH GLAUCOMA AND STEROID RESPONDERS.

PURPOSE: To assess the changes in intraocular pressure (IOP) after dexamethasone (DEX) implant in patients with glaucoma or history of steroid responders. METHODS: A retrospective study of patients who received DEX implant was conducted in a tertiary care center in India. Demographic details and IOP measurements at preinjection and postinjection were collected. The proportion of patients with and without IOP rise after DEX implant was noted, and the number of antiglaucoma medications to control the IOP was analyzed. The changes in IOP were also compared in the group with no glaucoma/steroid responder. RESULTS: A total of 815 patients, 767 patients in the nonglaucoma group and 48 patients in the glaucoma referral group, who underwent DEX implant were included in this study. The overall mean (SD) age of study participants was 56.3 (SD = 12.6) years. The overall mean (SD) IOP at baseline and at follow-up after injection for both nonglaucoma and glaucoma referral groups was found to be significant (P < 0.001). The differences in IOP measurements across follow-ups after DEX implant were found to be significant in both nonglaucoma (P < 0.001) and glaucoma referral groups (P < 0.001). Among the study patients in the IOP-rise group, 46.43% had maximum IOP rise in 1-week follow-up and 39% in 2-week follow-up, where 78.6% showed IOP controlled with 1 antiglaucoma medication. CONCLUSION: The rise in IOP after DEX implant was noted within first 2 weeks, which can be managed with topical antiglaucoma medications. Hence, with a close early follow-up monitoring of IOP, and timely medical intervention, DEX implant can be performed in patients with glaucoma.

[Relationships among illness perceptions, medication beliefs and medication adherence in primary angle closure glaucoma patients].

Objective: To investigate the relationships among illness perception, medication beliefs and medication adherence in primary angle closure glaucoma patients. Methods: It was a cross-sectional study. Morisky 8-item Medication Adherence Questionnaire Chinese Revised, the Brief Illness Perceptions Questionnaire, the Specific Section of the Beliefs about Medicine Questionnaire Chinese Revised were administered to 156 primary angle closure glaucoma patients from Tianjin Eye Hospital. Chi-square test was used to analyze the types of glaucoma, gender, prescription complexity, medicine schedule, other disease and course of disease between the group of adherence and non-adherence. Pearson correlation method was used to analyze the correlations among the illness perception, necessity belief, concerns belief and medication adherence. Structural equation model was used to analyze the mediational role of medication belief between illness perception and medication adherence. Results: In the 156 primary angle closure glaucoma patients being investigated, 37 male and 119 female, the average age was (61.3±8.3) years old. The medication adherence of patients was 83 (53.2%) , the medication non-adherence of patients was 73 (46.8%) . It was showed that prescription complexity and medicine schedule were significantly correlated with medicine adherence (χ(2)=13.64, 11.31; P<0.05); gender, other disease and course of disease were not correlated with medication adherence (χ(2)=1.02, 1.73, 6.08; P>0.05). The scores of illness perception were positively correlated with the necessity belief of medication scores, the scores of concerns belief (r=0.18、0.45, P<0.05), and were negatively associated with medication adherence (r=-0.22, P<0.01). The concerns belief of medication scores were negatively correlated with the medication adherence (r=-0.47, P<0.01). Concerns belief mediates the relationship between illness perception and medication adherence wholly (χ(2)/df=1.73, RMSEA=0.069, NNFI=0.98, CFI=0.98, IFI=0.98) . Conclusions: The types of medicines and the number of glaucoma medication used have a significant influence to the medication adherence in the patients with primary angle closure glaucoma. The patients with greater illness perception performed greater non-adherence can be explained by their higher concerns blief. (Chin J Ophthalmol, 2017, 53: 109-114).

Bilateral acute angle-closure glaucoma induced by duloxetine.

Introduction - To present a rare case of bilateral acute angle-closure glaucoma secondary to duloxetine administered for the treatment of depression. Case presentation - A 46 year old woman developed bilateral closed angle glaucoma after 15 days of duloxetine usage. Intraocular pressures (IOP) were 52 and 55 mm Hg in right and left eyes respectively, with shallow anterior chamber and angle closure on gonioscopy. Discontinuing duloxetine treatment, initiation of antiglaucomatous treatment and bilateral Nd:YAG Laser iridotomy obtained normalized IOP and anterior chamber depth. Conclusion - Duloxetine, used in the treatment of depression can be responsible for acute angle-closure glaucoma by leading to mydriasis and ciliary effusion.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Ocular safety of propiverine hydrochloride in elderly patients with primary open- and narrow-angle glaucoma
.

BACKGROUND: Propiverine hydrochloride (P4) is an antimuscarinic drug used in overactive bladder syndrome. METHODS: Two studies were performed: one in 24 patients with open-angle glaucoma (OAG) treated with topical ß-blockers, one in 24 patients with narrow-angle glaucoma (NAG) treated with pilocarpine ± topical ß-blockers. Patients were treated in randomized, placebo-controlled, double-blind parallel-group fashion (15 : 9 attribution to P4 vs. placebo (PL)). TREATMENTS: Single-blind PL dose in the morning of day 1 for baseline; double-blind 15 mg P4 or matched placebo t.i.d. from the afternoon of day 1 until the morning of day 7. RESULTS: In the morning of day 7, trough mean serum P4 concentrations were 169.4 ng/mL (CV (coefficient of variation): 0.55) and 140.7 ng/mL (CV: 0.56) in OAG and NAG; at 3:15 hours after dosing: 237.4 ng/mL (CV: 0.47) and 212.4 ng/mL P4 (CV: 0.38), respectively. P4-treatment led to a prompt (OAG) or more gradient (NAG) increase in pupil diameter (PUD), with a maximum difference from PL of 0.97 mm (95% confidence interval (CI): 0.67 - 1.27) and 0.87 mm (95% CI: 0.36 - 1.39) in OAG and NAG, respectively. However, there was no average increase in intraocular pressure (IOP) or increase in noteworthy safety-relevant individual IOP values (or changes thereof). There was no effect on visual acuity or accommodation. CONCLUSIONS: 1-week treatment with P4 appeared to be safe 1) in OAG patients treated with topical ß-blockers and 2) in NAG patients treated with topical pilocarpine ± ß-blockers, irrespective of whether the eyes had previously been treated with glaucoma surgery or laser therapy.
.

Multiplex cytokine levels of aqueous humor in acute primary angle-closure patients: fellow eye comparison.

BACKGROUND: The existing literature contains no information regarding inflammatory cytokine expression in unilateral acute primary angle-closure (APAC) affected eyes and fellow eyes with primary angle closure suspect (PACS). To measure levels of various inflammatory cytokines in the aqueous humor (AH) of APAC affected eyes and fellow eyes with a diagnosis of PACS (18 unilateral APAC eyes and 18 fellow eyes with PACS), and determine the underlying correlation between them. METHODS: The total levels of 12 cytokines including granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1ß, and vascular endothelial growth factor (VEGF) etc. were assessed using the multiplex bead immunoassay technique. The level of cytokines in different groups was analyzed by a 2-related-samples nonparametric test. Data on patient demographics, preoperative intraocular pressure (IOP), number of glaucoma medications, as well as several ocular biological parameters were also collected for correlation analysis. RESULTS: The APAC patients had significantly higher levels of G-CSF, IL-6, IL-8, MCP-1, MCP-3, MDC, MIP-1ß, and VEGF in the AH samples from unilateral APAC affected eyes than in fellow eyes with PACS (all P < 0.05). The cytokines showed positive correlations between each other (P < 0.0071). CONCLUSIONS: Cytokine networks in the AH may have critical roles in the progression of APAC. Thus, different cytokine expression in both eyes of the same patient may help us to understand the different pathology in APAC and PACS.

Glaucoma.

Glaucoma is a set of irreversible, progressive optic neuropathies that can lead to severe visual field loss and blindness. The two most common forms of glaucoma, primary open-angle glaucoma and primary angle-closure glaucoma, affect more than 2 million Americans and are increasing in prevalence. Many patients with glaucoma are asymptomatic and do not know they have the disease. Risk factors for primary open-angle glaucoma include older age, black race, Hispanic origin, family history of glaucoma, and diabetes mellitus. Risk factors for primary angle-closure glaucoma include older age, Asian descent, and female sex. Advanced disease at initial presentation and treatment nonadherence put patients with glaucoma at risk of disease progression to blindness. The U.S. Preventive Services Task Force has concluded that the evidence is insufficient to assess the potential benefits and harms of screening for glaucoma in the primary care setting. Regular eye examinations for adults are recommended by the American Academy of Ophthalmology, with the interval depending on patient age and risk factors. Diagnosis of glaucoma requires careful optic nerve evaluation and functional studies assessing a patient's visual field. The goal of treatment with eye drops, laser therapy, or surgery is to slow visual field loss by lowering intraocular pressure. Family physicians can contribute to lowering morbidity from glaucoma through early identification of high-risk patients and by emphasizing treatment adherence in patients with glaucoma.

[The effect of phacoemulsification on intraocular pressure in eyes with primary angle closure glaucoma after trabeculectomy].

OBJECTIVE: To evaluate the effect of phacoemulsification on intraocular pressure (IOP) in filtered eyes with primary angle closure glaucoma (PACG). METHODS: In this retrospective case series, 47 eyes from 47 PACG patients who previously had trabeculectomy were consecutively enrolled. All patients had visually significant cataracts and phacoemulsification was performed at least 3 months after trabeculectomy. The IOPs were recorded preoperatively, 1 day, 1 week, 2 weeks, 1 month, 3 months, 6 months, 12 months and 24 months after surgery. The best correct visual acuity (BCVA) , the number of glaucoma medications and the filtered bleb grade were recorded preoperatively and 24 months after phacoemulsification. IOP and BCVA before and after phacoemulsification were compared by student t test. The frequences of antiglaucoma medicine, bled grade and IOP control before and after phacoemulsification were compared by Mann-Whitney Test. Linear regression analysis, Pearson and Spearman were performed to assess the correlation between IOP change and other variants. RESULTS: IOP was decreased significantly from (18.7±6.7) mmHg (1 mmHg=0.133 kPa) at baseline to 16.4±2.0 mmHg at final follow-up (t=2.54, P=0.015) . The median number of glaucoma medications was significantly decreased (P<0.01) at 2 years postoperatively. The magnitude of IOP reduction was significantly correlated with preoperative IOP (r=0.95, P<0.01). BCVA (LogMAR) was improved significantly at month 24 (t=5.62, P<0.01). Filtered bleb decreased insignificantly at 2 years postoperatively (P=0.113). Complete success, qualified success and failure rates in terms of IOP were 61.7%, 27.7% and 10.6% before surgery , 89.4%, 8.5%, 2.1% at 2 years postoperatively. In 29 patients with preoperative IOP≤21 mmHg, mean IOP increased insignificantly from (14.5±4.0) mmHg to (15.5 ± 2.3) (P=0.195) at 2 years. In the 18 patients with preoperative IOP> 21 mmHg, mean IOP decreased from (25.3 ± 4.4) mmHg preoperatively to (17.8 ± 2.4) mmHg (P<0.01). CONCLUSIONS: Phacoemulsification reduces IOP and the number of glaucoma medications in previously filtered PACG eyes. The IOP remained normal in normal tension eyes after phacoemulsification in filtered PACG eyes but decreased significantly in hypertensive eyes.

Evaluating the long-term efficacy of short-duration 0.1 mg/ml and 0.2 mg/ml MMC in primary trabeculectomy for primary adult glaucoma.

OBJECTIVE: To evaluate safety and efficacy of 0.1 mg/ml versus 0.2 mg/ml mitomycin-C (MMC), applied for 1 min subconjunctivally, during trabeculectomy for primary adult glaucoma in previously un-operated eyes. MATERIALS AND METHODS: This is a randomised controlled, non-inferior, clinical trial consisting of 50 consecutive POAG or CPACG patients uncontrolled on maximal hypotensive therapy, meeting all inclusion criteria. Patients were randomized into two groups and underwent a standard limbus-based trabeculectomy with MMC: Group I, 0.1 mg/ml and Group II, 0.2 mg/ml. The pre-operative and post-operative intraocular pressure (IOP), bleb morphology, and visual acuity were recorded every 6 months for 2 years. Complete success (primary outcome) was defined as IOP ≤ 15 mmHg without any additional medications at the end of 2 years. RESULTS: The average age of patients was 62.6 ± 9.8 years and 61.2 ± 8.1 years in Group 1 and 2, respectively; p = 0.57. The mean preoperative IOP was 22.5 ± 1.4 mmHg and 23.3 ± 1.8 mmHg; p = 0.10. The mean IOP at 2 years was 11.1 ± 1.6 mmHg and 10.8 ± 2.8 mmHg, a mean reduction in IOP of 50.6 ± 1.23 %, and 53.7 ± 2.25 % in Group I and II, respectively. The complete success was 92.0 % and 91.7 % in the two groups, respectively (p = 0.99), and there was one failure (Group II, post trauma). A wider bleb extent and larger areas of thin, transparent conjunctiva over the bleb were seen with the 0.2 mg/ml MMC group (p < 0.001) and in PACG eyes; p < 0.04. CONCLUSION: A 1-min subconjunctival application of low dose 0.1 mg/ml MMC is non-inferior to 0.2 mg/ml and is probably a safer alternative, as thinning of the bleb is significantly less frequent in the long term.

Secondary angle closure glaucoma by lupus choroidopathy as an initial presentation of systemic lupus erythematosus: a case report.

BACKGROUND: We present a rare case of secondary angle closure glaucoma due to systemic lupus erythematosus choroidopathy as initial presentation of systemic lupus erythematosus, accompanied by central nervous system vasculitis and uncontrolled nephropathy. CASE PRESENTATION: A 31-year-old woman presented with decreased visual acuity, nausea, vomiting, fever, and bilateral angioedema-like eyelid swelling. She had persistent dry cough while taking medication for 3 months, and had usual posterior neck pain, which was treated with analgesic medication and Asian medicines. Intraocular pressure was 32 and 34 mmHg in her right and left eyes, respectively. Peripheral anterior chambers were shallow (grade I) using the van Herick method. Gonioscopy revealed 360° closed angle in both eyes. In both eyes, serous retinal detachment was found using optical coherence tomography and B scan ultrasonography, as well as choroidal thickening with effusion. Secondary acute angle closure glaucoma was drug induced, or caused by uveitis of unknown etiology when she was first treated with intraocular pressure-lowering medication. During evaluation of the drug-induced angioedema in the internal medicine department, systemic lupus erythematosus was diagnosed, based on malar rash, photosensitivity, proteinuria, and positive anti-Smith and anti-DNA antibodies, followed by initiation of steroid pulse therapy. Using fluorescein angiography, multifocal subretinal pinpoint foci were detected at the middle phase. We then diagnosed bilateral angle closure glaucoma by choroidal effusions, with lupus choroidopathy. At 2 months after steroid pulse therapy, subretinal fluid was not found, and visual acuity improved to normal. During the subsequent 2 years, lupus choroidopathy was not aggravated but lupus nephritis was not controlled. CONCLUSION: Patients with systemic lupus erythematosus choroidopathy can develop ciliochoroidal effusion, which can lead to acute angle closure glaucoma. Systemic lupus erythematosus choroidopathy is an early sign of severe complications. Angle closure glaucoma by systemic lupus erythematosus choroidopathy can be effectively treated using antiglaucoma drugs and immunosuppressive therapy.