Antioxidant nanoemulsion loaded with latanoprost enables highly effective glaucoma treatment.

Glaucoma is the third leading cause of blindness worldwide and is primarily characterized by elevated intraocular pressure (IOP). Common risk factors such as age, myopia, ocular trauma, and hypertension all increase the risk of elevated IOP. Prolonged high IOP not only causes physiological discomfort like headaches, but also directly damages retinal cells and leads to retinal ischemia, oxidative imbalance, and accumulation of reactive oxygen species (ROS) in the retina. This oxidative stress causes the oxidation of proteins and unsaturated lipids, leading to peroxide formation and exacerbating retinal damage. While current clinical treatments primarily target reducing IOP through medication or surgery, there are currently no effective methods to mitigate the retinal cell damage associated with glaucoma. To address this gap, we developed a novel nanoemulsion to co-delivery latanoprost and α-tocopherol (referred to as LA@VNE later) that prolongs ocular retention and enhances retinal permeability through localized administration. By encapsulating latanoprost, an IOP-lowering drug, and α-tocopherol, a potent antioxidant, we effectively reduced ROS accumulation (>1.5-fold in vitro and 2.5-fold in vivo), retinal ganglion cell (RGC) apoptosis (>9 fold), and inflammatory cell infiltration (>1.6 fold). Our approach showed strong biocompatibility and significant potential for clinical translation, providing a promising platform for the treatment of glaucoma.

Prostaglandin analogs in ophthalmology.

Glaucoma is a major cause of irreversible blindness worldwide. Reducing intraocular pressure (IOP) is currently the only approach to prevent further optic nerve head damage. Pharmacotherapy is the mainstay of treatment for glaucoma patients. In recent years, a significant milestone in glaucoma treatment has been a transition to prostaglandin analogs (PGAs) as the first line of drugs. The rapid shift from traditional ß-blockers to PGAs is primarily due to their excellent efficacy, convenient once-a-day usage, better diurnal control of IOP, and systemic safety profiles. This review article aims to provide information regarding the various PGAs in practice and also the newer promising drugs.

The effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% at a tertiary glaucoma center.

PURPOSE: To assess real-world effectiveness and tolerability of fixed-dose combination netarsudil 0.02%/latanoprost 0.005% (FCNL) in management of glaucoma patients in a tertiary eye care center. METHODS: This retrospective cohort study included glaucoma patients initiated on FCNL from January 2018 to July 2021 with at least 1-month follow-up. Demographic and clinical data were collected at baseline and at follow-up visits through 12 months. Patient-solicited side effects were recorded at each visit. Maximum glaucoma pharmacotherapy was defined as surgery/laser being the next treatment option following an intensive pharmacotherapy regimen, or when pharmacotherapy could not be increased due to allergy/intolerance or all pharmacologic mechanisms already being in use. RESULTS: Seventy-nine eyes of 47 patients were included. Mean age was 67.7 ± 14.7 years. Baseline IOP was 18.7 ± 4.9 mmHg; mean change in IOP (∆IOP) each study visit compared to baseline ranged from - 1.6 ± 3.5 to - 4.4 ± 4.1 mmHg (all p < 0.05). The eyes on maximum glaucoma pharmacotherapy (73.4%) had similar ∆IOP compared to those on non-maximal therapy at each visit (p > 0.2 for all). Forty-three (54.4%) eyes were switched from a prostaglandin analog alone, producing a 1-month IOP reduction of - 4.7 ± 3.9 mmHg at 1 month which remained significant at each visit for the 12-month study period (all p < 0.05). Across all study visits, conjunctival hyperemia was documented in 26 (32.9%) eyes. Subjective blurry vision was reported in 22 (27.8%) eyes without significant worsening of visual acuity at any visit (all p > 0.05). Six (7.6%) and 7 (8.9%) eyes required further medical or surgical/laser intervention, respectively. Kaplan-Meier analysis revealed no significant difference in the need for subsequent medical or surgical intervention between those on maximum and non-maximal pharmacotherapy (p > 0.4). CONCLUSION: FCNL was well-tolerated and demonstrated a significant and sustained reduction in IOP, even as last-line therapy before incisional or laser surgery in those on maximum glaucoma pharmacotherapy. FCNL is a viable treatment option for glaucomatous eyes before consideration of surgical intervention.

Advances in medical therapy for glaucoma.

PURPOSE OF REVIEW: To discuss a new class of medication that has recently become available for the treatment of glaucoma; as well as share insights into developments in glaucoma medicine administration which has the potential to revolutionize medical therapy for glaucoma. RECENT FINDINGS: Newly available eye drops, netarsudil 0.02% and latanoprostene bunod 0.024%, are improving aqueous outflow through the conventional outflow tract. Other new developments in medical glaucoma are focused on alternative methods for sustained glaucoma medication delivery. SUMMARY: Newer medications may be able to extend the duration of medically controlled glaucoma, delaying or possibly eliminating the need of glaucoma surgery for some patients. Alternative methods of delivery for glaucoma medications may be a key factor in improving outcomes with currently available medications.

New Drugs 2018, part 3.

This article discusses eight drugs recently approved by the FDA, including their indications and contraindications, precautions, dosage, and nursing considerations. The article also includes summary charts on 14 recently approved antineoplastic drugs and four drugs approved for rare disorders.

The Glaucoma Italian Pediatric Study (GIPSy): 1-Year Results.

PURPOSE: To investigate the efficacy and safety of a treatment strategy with latanoprost and dorzolamide in primary pediatric glaucoma patients partially responsive to surgery. PATIENTS AND METHODS: Children with primary pediatric glaucoma having postsurgical untreated intraocular pressure (IOP) between 22 and 26 mm Hg were eligible. At baseline, patients were administered latanoprost once daily. Depending on IOP reduction, patients were allocated to continuation of latanoprost monotherapy or addition of dorzolamide twice daily, or switch to dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy group with IOP reduction <20% from baseline were considered nonresponders. The primary endpoint was the percentage of responders. Study treatment continued for 3 years or until treatment failure. The present article reports the 1-year analysis results. RESULTS: A total of 35 patients (57 eyes) were analyzed. The mean age was 4.0 years (SD, 3.8). In total, 51 eyes were included in the efficacy analysis. In total, 43 eyes (84.3%; 95% confidence interval, 74.3-94.3) were considered responders: 29 on latanoprost monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely related to the age at the time of surgery. IOP reduction was 8.7 mm Hg (SD, 2.2) for latanoprost, 7.5 mm Hg (SD, 1.4) for the latanoprost/dorzolamide combination, and 8.7 mm Hg (SD, 2.1) for the dorzolamide monotherapy. Only mild or moderate local adverse events were noted. None of the patients was withdrawn due to adverse events. CONCLUSION: Latanoprost alone or in combination with dorzolamide is safe and highly effective in lowering IOP in children postsurgery. Nonresponders were mainly patients with early presentation of the disease.

Factors Related to Prostaglandin-Associated Periorbitopathy in Glaucoma Patients.

PURPOSE: To determine factors related to prostaglandin-associated periorbitopathy (PAP) and its prevalence in glaucoma or ocular hypertension (OHT) patients using prostaglandins analogs (PGAs). DESIGN: A cross-sectional study. METHODS: A study of glaucoma or OHT patients, using topical PGAs for at least 3 months, was performed. Eyes treated with PGAs were photoraphed and independently evaluated for PAP by 2 glaucoma specialists using at least 4 out of 7 clinical appearances. The factors of interest were sex, age, body mass index (BMI), types of glaucoma, types of PGAs, duration of PGA use, and concurrent 0.5% timolol. Univariate (χ2 test) and multivariate (multiple logistic regression) analyses assessing risk factors for PAP were performed to estimate the odds ratios (OR) with 95% conidence intervals (CIs). RESULTS: One hundred thirty-four eyes from 134 patients were included. Seventy (52.2%), 21 (15.7%), and 43 (32%) eyes received components of latanoprost, travoprost, and bimatoprost, respectively. Prevalence of PAP was 44.8% (95% CI, 36.3 to 53.3). Older age >60 years (OR, 3.0; 95% CI, 1.2 to 7.8), bimatoprost (OR, 4.0; 95% CI, 1.6 to 9.5), travoprost (OR, 3.3; 95% CI, 1.1 to 10.1), and timolol (OR, 2.9; 95% CI, 1.3 to 6.8) were at risk of PAP development. In addition, BMI ≥23 kg/㎡ (OR, 0.3; 95% CI, 0.1 to 0.7) was reversely associated with PAP. CONCLUSIONS: Older age, bimatoprost, or travoprost were associated with PAP, whereas high BMI was found as a protective factor. Interestingly, timolol possibly precipitated periorbital change when in use with prostaglandins.

Novel Pharmacologic Candidates for Treatment of Primary Open-Angle Glaucoma.

Primary open-angle glaucoma (OAG) affects approximately 45 million people worldwide and more than 2.5 million people aged 40 years or older in the United States. Pharmacologic treatment for glaucoma is directed towards lowering intraocular pressure (IOP) to slow disease progression and delay visual field loss. Current medical treatment options for the lowering of IOP include the following classes of topical medications: beta-adrenergic antagonists, alpha-adrenergic agonists, cholinergic agonists, carbonic anhydrase inhibitors, and prostaglandin analogs. Issues with existing drugs include failure to achieve target IOP with monotherapy, drug-related side effects, and low patient compliance with multiple daily administration of eye drops. In recent years, the scientific and medical community has seen encouraging development of novel classes of drugs for primary OAG, the majority of which lower IOP by targeting the trabecular meshwork outflow pathway to increase aqueous humor outflow. Among the most promising new pharmacologic candidates are rho kinase inhibitors including ripasudil (K-115), netarsudil (AR-13324), and AMA0076; adenosine receptor agonists including trabodenoson (INO-8875); and modified prostaglandin analogs including latanoprostene bunod (LBN, BOL-303259-X) and ONO-9054. This study aims to systematically review and summarize the most recent developments in clinical trials for new pharmacologic options for the treatment of primary open-angle glaucoma.

Intraocular Pressure-Lowering Effect of Latanoprost Is Hampered by Defective Cervical Lymphatic Drainage.

PURPOSE: To evaluate whether defects in cervical lymphatic drainage influence the intraocular pressure (IOP)-lowering effect of latanoprost in patients with primary open-angle glaucoma (POAG) who have undergone unilateral radical neck dissection (uRND). METHODS: We enrolled (1) bilateral POAG patients who had started (bilateral) latanoprost (0.005%) monotherapy prior to their uRND and (2) treatment-naïve, bilateral glaucoma suspects (GSs) who had undergone the same surgery. We compared the eyes ipsilateral to the uRND with their fellow eyes in terms of the changes in IOP between the baseline (prior to the uRND) and the follow-up visits (1, 3, and 6 months after the uRND). RESULTS: The study involved 22 eyes of 11 POAG patients and 14 eyes of 7 GSs. In the POAG patients, IOP had increased significantly after surgery in the eyes ipsilateral to the uRND (from 14.7±1.4mmHg to 17.1±2.2mmHg; P = 0.007). Interestingly, in the eyes contralateral to the uRND, IOP had not changed significantly after surgery (from 14.2±1.8mmHg to 14.4±2.0mmHg; P = 0.826). In GSs, the eyes ipsilateral to the uRND did not differ significantly from their fellow eyes in terms of post-operative IOP change (ipsilateral value: 0.3±0.5mmHg, fellow eyes: -0.1±0.7mmHg; P = 0.242). CONCLUSION: In the POAG patients, IOP had increased significantly in the eyes ipsilateral to the uRND. However, it had not changed significantly in the eyes contralateral to the surgery or in the eyes of the GSs. These findings suggest that, latanoprost works, at least in part, by enhancing outflow from the aqueous humor via the uveolymphatic pathway.

Eye problems in a woman with Churg-Strauss syndrome.

Churg-Strauss syndrome is a rare, systemic vasculitis of unknown cause. Ocular involvement is a rare but established complication and can lead to vision damage or blindness if not treated promptly. Treatment of ocular manifestations corresponds with systemic treatment of the disease and consists primarily of corticosteroids.

New classes of glaucoma medications.

PURPOSE OF REVIEW: To discuss recent advances in the medical management of glaucoma and to highlight future medical therapies currently in development. RECENT FINDINGS: In 1996, latanoprost (Xalatan) was approved in the United States as a new chemical entity and new class (prostaglandin analogs) for the topical treatment of ocular hypertension and glaucoma. In the period from the late 1990s-2010s, while there were additional new chemical entities, fixed dose combinations, and formulation improvements, there were no new classes of ocular hypotensive medications approved worldwide. We summarize new pharmacological treatments that are currently in clinical trials - new classes, new molecules and new delivery systems. SUMMARY: Although challenges in medical treatment of glaucoma exist, particularly in patient adherence, medical therapy remains the first line treatment for almost all glaucoma patients. Few new medications for glaucoma therapy are currently available for our patients, but multiple drugs with novel mechanisms of action, new formulations, and new delivery mechanisms are currently in development.

The neuroprotective effect of latanoprost acts via klotho-mediated suppression of calpain activation after optic nerve transection.

Latanoprost was first developed for use in glaucoma therapy as an ocular hypotensive agent targeting the prostaglandin F2α (FP) receptor. Subsequently, latanoprost showed a neuroprotective effect, an additional pharmacological action. However, although it is well-known that latanoprost exerts an ocular hypotensive effect via the FP receptor, it is not known whether this is also true of its neuroprotective effect. Klotho was firstly identified as the gene linked to the suppression of aging phenotype: the defect of klotho gene in mice results aging phenotype such as hypokinesis, arteriosclerosis, and short lifespan. After that, the function of klotho was also reported to maintain calcium homeostasis and to exert a neuroprotective effect in various models of neurodegenerative disease. However, the function of klotho in eyes including retina is still poorly understood. Here, we show that klotho is a key factor underlying the neuroprotective effect of latanoprost during post-axotomy retinal ganglion cell (RGC) degeneration. Importantly, a quantitative RT-PCR gene expression analysis of klotho in sorted rat retinal cells revealed that the highest expression level of klotho in the retina was in the RGCs. Latanoprost acid, the biologically active form of latanoprost, inhibits post-traumatic calpain activation and concomitantly facilitates the expression and shedding of klotho in axotomized RGCs. This expression profile is a good match with the localization, not of the FP receptor, but of organic anion transporting polypeptide 2B1, known as a prostaglandin transporter, in the ocular tissue. Furthermore, an organic anion transporting polypeptide 2B1 inhibitor suppressed latanoprost acid-mediated klotho shedding ex vivo, whereas an FP receptor antagonist did not. The klotho fragments shed from the RGCs reduced the intracellular level of reactive oxygen species, and a specific klotho inhibitor accelerated and increased RGC death after axotomy. We conclude that the shed klotho fragments might contribute to the attenuation of axonal injury-induced calpain activation and oxidative stress, thereby protecting RGCs from post-traumatic neuronal degeneration.

PTGFR and SLCO2A1 Gene Polymorphisms Determine Intraocular Pressure Response to Latanoprost in Han Chinese Patients with Glaucoma.

PURPOSE: To determine the relationship between the polymorphisms of the prostaglandin F2α receptor (PTGFR) and solute carrier organic anion transporter family 2A1 (SLCO2A1) genes and response to latanoprost treatment in Han Chinese patients with glaucoma. MATERIALS AND METHODS: 89 patients with POAG or OH received latanoprost treatment and intraocular pressure (IOP) data was collected on day 7 and day 30. The rs12093097, rs35586449, rs3753380, and rs3766355 single-nucleotide polymorphisms (SNPs) in the PTGFR gene and rs2370512, rs34550074, and rs4241366 SNPs in the SLCO2A1 gene were analyzed using direct DNA sequencing or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The IOP in patients with GG allele of rs4241366 was lower than in patients with GC+CC on day 7 (p = 0.007). The IOP in patients with CC allele of rs3766355 was lower than in patients with CA+AA on day 30 (p = 0.024). Multiple regression analysis demonstrated that even after adjusting for baseline IOP, the rs4241366 in SLCO2A1 gene and the rs3766355 in PTGFR gene correlated with response to latanoprost on day 7 (rs4241366, p = 0.014) and day 30 (rs3766355, p = 0.035), respectively, in Han Chinese patients with glaucoma. CONCLUSIONS: An association was found between single nucleotide polymorphisms of the PTGFR and SLCO2A1 genes and the response to latanoprost in Han Chinese patients with glaucoma. These SNPs may be important determinants of differential response to latanoprost.

Medical Functions of Hydrogen Sulfide.

Hydrogen sulfide (H(2)S) is a gasomediator synthesized from L- and D-cysteine in various tissues. It is involved in a number of physiological and pathological processes. H(2)S exhibits antiatherosclerotic, vasodilator, and proangiogenic properties, and protects the kidney and heart from damage following ischemia/reperfusion injury. H(2)S donors may be natural or synthetic, and may be used for the safe treatment of a wide range of diseases. This review article summarizes the current state of knowledge of the therapeutic function of H(2)S.

The effects of topical parasympatholytic drugs on pupil diameter and intraocular pressure in healthy dogs treated with 0.005% latanoprost.

PURPOSE: Prostaglandin analogs induce miosis and lower intraocular pressure (IOP). As pupils of latanoprost-treated eyes may have to be dilated for ophthalmoscopy or intraocular surgery, we studied whether 0.5% tropicamide or 1% atropine alter the effects of 0.005% latanoprost on pupil diameter (PD) and IOP in healthy dogs. METHODS: IOP and PD were measured hourly, 8 AM-4 PM, with the right and left eyes serving as control (CE) and treated (TE) eyes, respectively. Measurements were conducted in ten Labrador retrievers with one-week washout: (i) baseline values, (ii) latanoprost at 8 AM, (iii) tropicamide at 8 AM, (iv) latanoprost at 8 AM and tropicamide at 11 AM, and (v) latanoprost at 8 AM and atropine at 11 AM (n = 4). RESULTS: At 4 PM, TE PD was 5.88 ± 0.59, 3.62 ± 0.66, 6.33 ± 1.00, 5.42 ± 0.57, and 8.12 ± 1.24 mm in sessions 1-5, respectively. TE PD was significantly different between treatment sessions 2, 4, and 5 (P = 0.018, Friedman), being most mydriatic in session 5. At 4 PM, TE IOP was 11.27 ± 2.07, 7.10 ± 1.07, 11.1 ± 2.21, 7.70 ± 1.85, and 8.87 ± 1.42 mm Hg in sessions 1-5, respectively, with no differences between treatment sessions 2, 4, and 5 (P = 0.105, Friedman). CONCLUSIONS: Tropicamide and atropine counteracted latanoprost's miotic effect, with atropine causing significantly larger mydriasis, sufficient for indirect ophthalmoscopy. Neither drug counteracted the hypotensive effect of latanoprost during this study period. Further studies are necessary to evaluate the potential risks in glaucomatous dogs.

Selective modulation of the prostaglandin F2α pathway markedly impacts on endometriosis progression in a xenograft mouse model.

STUDY HYPOTHESIS: Selective activation or blockade of the prostaglandin (PG) F2α receptor (FP receptor) affects ectopic endometrial tissue growth and endometriosis development. STUDY FINDING: FP receptor antagonists might represent a promising approach for the treatment of peritoneal endometriosis. WHAT IS KNOW ALREADY: Eutopic and ectopic endometrium from women with endometriosis exhibit higher expression of key enzymes involved in the PGF2α biosynthetic pathway. It has also been shown that the PGF2α-FP receptor interaction induces angiogenesis in human endometrial adenocarcinoma. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: For this study, a mouse model of endometriosis was developed by inoculating human endometrial biopsies into the peritoneal cavity of nude mouse (n = 15). Mice were treated with AL8810 (FP receptor antagonist), Fluprostenol (FP receptor agonist) or PBS. Endometriosis-like lesions were collected and analysed for set of markers for angiogenesis, tissue remodelling, apoptosis, cell proliferation and capillary formation using qPCR and immunohistochemistry. MAIN RESULTS AND THE ROLE OF CHANCE: We found that selective inhibition of the FP receptor with a specific antagonist, AL8810, led to a significant decline in the number (P < 0.01) and size of endometriosis-like lesions (P < 0.001), down-regulated the expression of key mediators of tissue remodelling (MMP9, P < 0.05) and angiogenesis (VEGF, P < 0.01) and up-regulated the pro-apoptotic factor (Bax, P < 0.01) as compared with controls. Immunohistochemical analyses further showed a marked decrease in cell proliferation and capillary formation in endometrial implants from AL8810-treated mice, as determined by proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) immunostaining, respectively. Moreover, Fluprostenol, a selective FP receptor agonist, showed the opposite effects. LIMITATIONS, REASONS FOR CAUTION: We carried out this study in nude mice, which have low levels of endogenous estrogens which may affect the lesion growth. Caution is required when interpreting these results to women. WIDER IMPLICATIONS OF THE FINDINGS: This study extends the role of PG signalling in endometriosis pathogenesis and points towards the possible relevance of selective FP receptor antagonism as a targeted treatment for endometriosis. LARGE SCALE DATA: Not Applicable. STUDY FUNDING AND COMPETING INTERESTS: This work was supported by grant MOP-123259 to the late Dr Ali Akoum from the Canadian Institutes for Health Research. The authors have no conflict of interest.

Late postoperative choroidal detachment following an uneventful cataract surgery in a patient on topical latanoprost.

Topical latanoprost is a most effective and commonly used antiglaucoma medication. Use of prostaglandin analogues (PGA) in the early postoperative period is controversial due to its proinflammatory properties. We report a case of a 64-year-old man with primary open angle glaucoma, post-trabeculectomy 17 years prior, with good intraocular pressure (IOP) control on topical levobunolol 0.5% and latanoprost 0.005%. He underwent a clear corneal phacoemulsification surgery in his left eye and the PGA was stopped. He had an uneventful postoperative course and was prescribed eyeglasses at 4-week follow-up. Two weeks later, he presented to the emergency department with decreased vision in the left eye, flat anterior chamber, IOP of 00 mm Hg and 360° choroidal detachment. The continued use of topical latanoprost in the operated eye was implicated as the cause. This case illustrates the serious vision-threatening side effect of PGA when used in the early postoperative period.

Development of a novel injectable drug delivery system for subconjunctival glaucoma treatment.

In this study we present the development of an injectable polymeric drug delivery system for subconjunctival treatment of primary open angle glaucoma. The system consists of hyaluronic acid sodium salt (HA), which is commonly used in ophthalmology in anterior segment surgery, and an isocyanate-functionalized 1,2-ethylene glycol bis(dilactic acid) (ELA-NCO). The polymer mixtures with different ratios of HA to ELA-NCO (1/1, 1/4, and 1/10 (v/v)) were investigated for biocompatibility, degradation behavior and applicability as a sustained release system. For the latter, the lipophilic latanoprost ester pro-drug (LA) was incorporated into the HA/ELA-NCO system. In vitro, a sustained LA release over a period of about 60days was achieved. In cell culture experiments, the HA/ELA-NCO (1/1, (v/v)) system was proven to be biocompatible for human and rabbit Tenon's fibroblasts. Examination of in vitro degradation behavior revealed a total mass loss of more than 60% during the observation period of 26weeks. In vivo, LA was continuously released for 152days into rabbit aqueous humor and serum. Histological investigations revealed a marked leuko-lymphocytic infiltration soon after subconjunctival injection. Thereafter, the initial tissue reaction declined concomitantly with a continuous degradation of the polymer, which was completed after 10months. Our study demonstrates the suitability of the polymer resulting from the reaction of HA with ELA-NCO as an injectable local drug delivery system for glaucoma therapy, combining biocompatibility and biodegradability with prolonged drug release.

Prostaglandin agonist effect on matrix metalloproteinase aqueous levels in glaucoma patients.

OBJECTIVE: To determine whether the aqueous levels of matrix metalloproteinases (MMPs) differ between patients with glaucoma treated with topical prostaglandin analogues and normal, nonglaucomatous control patients. Also, to note any difference in MMP levels between latanoprost, travoprost, and bimatoprost that might suggest a difference in efficacy or mechanism of action between these drugs. DESIGN: Prospective, observational study. PARTICIPANTS: Patients who were scheduled to undergo routine intraocular surgery (phacoemulsification or combined phacotrabeculectomy) as part of their standard clinical care were included. Eighteen eyes of 18 patients with glaucoma using any 1 prostaglandin analogue (latanoprost, travoprost, or bimatoprost) were compared with 8 normal control patients. METHODS: This was a multicentre study. Aqueous humour (0.2 mL) was aspirated at the beginning of the intraocular surgery through a clear corneal paracentesis. MMP-2 and -9 were quantified in the aqueous of all participants using enzyme-linked immunosorbent assay. RESULTS: There was no significant difference in the levels of either MMP-2 (p = 0.216) or MMP-9 (p = 0.552) between the control patients and the patients with glaucoma on prostaglandins. There was no difference in the levels of MMP-2 or -9 between the latanoprost, travoprost, or bimatoprost groups. CONCLUSIONS: The levels of MMP-2 and -9 in aqueous of glaucomatous eyes on topical prostaglandin analogues were the same as those of normal age-matched control patients. This could reflect either a return to normal levels with efficacious treatment or a lack of difference between disease and nondisease states.

Guidelines for treatment of chronic primary angle-closure glaucoma.

OBJECTIVE: To present a clinical practice guideline update on the medical, laser, and surgical treatment of primary angle closure glaucoma (PACG) in adults. METHODS: Following the formulation of key questions using the PICO scheme (Patient/Problem, Intervention, Comparison, Outcome), a systematic review was performed on the literature published to date, including international clinical practice guidelines. The AMSTAR and Risk of Bias tools were used for evaluating the quality of the information. The level of evidence and grade of recommendation was established following the Scottish Intercollegiate Guidelines Network (SIGN) system. RESULTS: Following the above methodology, recommendations of medical, laser and surgical treatment in adult PACG and levels of evidence are presented. CONCLUSIONS: Although the level of scientific evidence for many of the questions raised is not very high, a review is presented on updated treatment recommendations for adult PACG. Among the limitations for the implementation of these recommendations is that most studies have been conducted in Asian populations, and that the effectiveness is measured almost exclusively in terms of reducing intraocular pressure, and does not include visual function, quality of life or cost-effectiveness parameters.