Progression Of Primary Open-angle Glaucoma Research Articles

Biomarkers and special features of oxidative stress in the anterior segment of the eye linked to lens cataract and the trabecular meshwork injury in primary open‐angle glaucoma: challenges of dual combination therapy with N‐acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine

The implication of oxidative stress associated with increased oxidant production in mammalian and human cells characterized by the release of free radicals, resulting in cellular degeneration, is involved in many ocular diseases, such as age-related macular degeneration, retinopathy of prematurity, retinal light damage, primary open-angle glaucoma (POAG), and cataract. Cataract is the leading cause of blindness, accounting for 50% of blindness worldwide. Glaucoma, the leading cause of irreversible blindness, is considered as a progressive optic neuropathy often caused by elevated intraocular pressure (IOP) consequent to abnormally high resistance to aqueous humor (AH) drainage via the trabecular meshwork (TM) and Schlemm's canal. Morphological and biochemical analyses of the TM of patients with POAG revealed the loss of cells, increased accumulation of extracellular matrix proteins (ECM), changes in the cytoskeleton, cellular senescence, and the process of subclinical inflammation. The TM is the target tissue of glaucoma in the anterior chamber, and the development and progression of glaucoma are accompanied by the accumulation of oxidative damage in this tissue. The separate studies were conducted to comparatively evaluate the sensitivity to oxidative stress and lipid peroxidation (LPO) of anterior chamber tissues including TM. Accumulation of the primary, secondary, and end products of LPO (diene and triene conjugates, Schiff's bases) was noted in the studied extracts. Significant differences in the levels of all mentioned LPO products in comparison with the control were observed. The data may be considered as an evidence of LPO participation in the destruction of the trabecule and Schlemm's canal in POAG. Treatment of TM cells with oxidative stress induced POAG-typical changes such as ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence, and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin analogs, beta-blockers, or local carbonic anhydrase inhibitors, these effects were markedly reduced. Oxidative stress can induce characteristic glaucomatous TM changes, and these oxidative stress-induced TM changes can be minimized by the use of antioxidants and IOP-lowering substances. It is tempting to speculate that the prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG. The author's laboratory has developed and patented the dual combination therapy with N-acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed carnosine in ripe cataracts and POAG. The specific regimen for the treatment in each stage of age-related ophthalmic disease has been taken up. In the treatment of POAG, this dual therapy can be combined with conventional antiglaucoma therapy with beta-blocking and/or adrenergic agonist medicines providing the significant IOP-lowering effect and significant increase in outflow facility. The developed therapy is a prominent management care of the glaucomatous neurodegeneration.

Peripapillary Retinoschisis in High Myopia: A Novel Clinical Entity Revealed by SD-OCT

We reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG.We searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio).Out of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched.AH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression.

HLA class I haplotypes and progression of primary open-angle glaucoma

To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8) associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field) of 25 patients (six of them with one of the haplotypes associated with glaucoma) followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP) for ten years after typing of their HLA antigens in order to compare with their previous condition. A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.

Alternative therapy in glaucoma management: Is there any role?

Glaucoma is one of the leading causes of blindness worldwide. Various randomized controlled clinical trials have shown that lowering intraocular pressure (IOP) does reduce progression of primary open-angle glaucoma. However, there is lots of interest in nonpharmacological options that includes lifestyle adjustment and alternative and complementary therapy (ACT). At least 5% glaucoma population uses ACT. Various lifestyle activities like exercise and alcohol can reduce IOP by 1 to 2 mm Hg but would have small effect on glaucoma. The psychological stress can increase IOP. Hypothetically and few studies do show neuroprotective effect (or effect on ocular blood flow) of alcohol, Gingko biloba, bilberry, but the current evidence is weak for its routine use. We must also remember the side effects of ‘medications’ (e.g., marijuana, alcohol) before promoting as remedy for glaucoma. In current armamentarium of glaucoma management, ACT cannot substitute the conventional treatment available to lower IOP.

Brain-Derived Neurotrophic Factor as a Biomarker in Primary Open-Angle Glaucoma

To introduce a novel biomarker for screening of primary open-angle glaucoma (POAG) by detecting and measuring brain-derived neurotrophic factor (BDNF) in the serum of normal subjects and patients with early stage of glaucoma. Twenty-five glaucoma patients as the case group and 25 age- and sex-matched normal persons as the control group were tested. The control group comprised 19 men and 6 women, with the mean age of 59.32 ± 11.8 years and without any apparent ocular or systemic diseases. The case group comprised 20 men and 5 women, with the mean age of 59.64 ± 11.56 years, who were assessed by routinely performed clinical and paraclinical investigations. BDNF levels in serum were determined by enzyme-linked immunosorbent assay using monoclonal antibodies specific for BDNF. The mean of BDNF levels in the serum was 27.16 ± 5.53 ng/mL in the control subjects and 18.42 ± 4.05 ng/mL in the subjects with the early stage glaucoma. A statistically significant difference was evident between the two groups (p < 0.05). We found no significant differences in serum BDNF levels according to the subjects' age, gender, duration of the glaucoma, mean intraocular pressure, and blood pressure (p > 0.05). Glaucoma patients who had lower serum BDNF concentration had disclosed a significant negative correlation with pattern standard deviations. We conclude that BDNF in the serum might be a useful biochemical marker for early detection of POAG. We also propose that this might be a reliable, time efficient, and cost-effective method for diagnosis, screening, and assessing the progression of POAG. However, more studies and trials are needed to investigate these factors in greater detail.

Methodologic Quality of Studies on Prognostic Factors for Primary Open-angle Glaucoma Progression Measured by Visual Field Deterioration

Glaucoma is a chronic, slowly progressing, and asymptomatic optic neuropathic disorder with a great variety of causes that involve gradual retinal ganglion cell axon loss. The disease is the second most common cause of blindness in the industrialized world. Once vision loss develops it is irreversible-although in many cases further loss can be slowed if adequate treatment is provided. If not treated, glaucoma can lead to complete vision loss in the affected eye. Primary open-angle glaucoma (POAG) is the most prevalent form of the disease in the industrialized countries, representing 94% of all glaucomas. In a Spanish study of 569 individuals, the prevalence of POAG was 2.1% (99% confidence interval 1.9%-2.3%) in the age range between 40 and 79 years. Assessing glaucomatous damage progression remains one of the most important and challenging aspects in glaucoma management. In addition, a better understanding of clinical risk factors for glaucoma worsening may help us to develop new strategies to improve glaucoma care. Over the past 2 decades, many studies have addressed the issue of risk factors associated with or predicting for glaucoma progression. Although many studies have attempted to identify the prognostic factors capable of predicting the course of POAG, the results have been varied and in some cases contradictory, and are thus of scant practical utility. This study was designed to evaluate the methodologic quality of the studies published in the literature on the prognostic factors for POAG progression measured by visual field deterioration.

Transforming growth factor-β2 levels in the aqueous humor of patients with primary open angle glaucoma and primary angle closure glaucoma

Background Transforming growth factor-beta2 (TGF-β2) has been implicated in the pathogenesis of glaucoma by its ability to induce extracellular matrix and many other changes. This study was designed to investigate the levels of TGF-β2 in the aqueous humor of patients with glaucoma, including correlations with intraocular pressure (IOP). Methods The study population comprised 15 patients with primary open angle glaucoma (POAG) and 15 patients with primary angle closure glaucoma (PACG) who had undergone trabeculectomy. Fifteen patients with senile cataract were recruited as control subjects. The levels of TGF-β2 in the aqueous humor were measured with an enzyme-linked immunosorbent assay (ELISA) and immunoblotting. In addition, the relationships with the glaucoma subtypes and IOP were analyzed. Results A significantly higher concentration of TGF-β2 was detected in POAG patients as compared to PACG patients as well as control subjects. Relationships between the TGF-β2 concentration and the intraocular pressure were not found significant. Conclusions TGF-β2 levels were significantly higher in the POAG group than in PACG and cataract group. The results suggest that TGF-β2 plays a key role in the pathogenesis and progression of POAG.

Long-Term Benefit of Reduced Intraocular Pressure in Primary Open-Angle Glaucoma Patients in Ethiopia

To determine the incidence of progression of primary open-angle glaucoma at individual levels of mean intraocular pressure (IOP) in patients in Ethiopia. A retrospective, multicenter, cohort analysis of patient records with at least 5 years of potential follow-up were evaluated for risk factors associated with progressive optic disc and visual field loss. There were 300 patients with the potential of 5 years of follow-up. In total, 166 patients progressed before 5 years and 134 remained stable for the full 5-year follow-up period. Of the total sample, 84% of patients with IOPs < or =19 (n=117/139), 53% of patients with IOPs of 20 (n=9/17), 14% of patients with IOPs of 21-24 (n=9/63), and 0% of the patients with IOPs of > or =25 mmHg (n=0/79) remained stable over at least 5 years. The mean IOP was 17.4+/-2.1 in the stable group and 25.0+/-5.9 mmHg in the progressed group (p<0.0001). The highest average peak IOP was 24.5+/-4.5 in the stable group and 29.0+/-6.1 mmHg in the progressed group (p<0.0001). A multivariant regression analysis to determine risk factors for progression was positive for mean IOP (p=0.0097). This study suggests that IOP reduction in a developing country, despite potential limitations in diagnostic techniques, follow-up, and compliance, can be effective in reducing the risk of glaucomatous progression over long-term follow-up.

Oxidativer Stress im Trabekelwerk beim POWG

Primary open angle glaucoma (POAG) is defined as an optic neuropathy which is characterised by the loss of optic nerve axons and the related retinal ganglion cells. The reason for these changes is still unknown. In the pathogenesis of POAG several factors like increased intraocular pressure and a reduction of ocular blood supply are discussed. Morphological and biochemical analyses of the trabecular meshwork (TM) of POAG patients revealed loss of cells, increased accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular senescence and the process of subclinical inflammation. One factor becoming more likely to be involved in the pathogenesis of POAG is oxidative stress. Treatment of TM cells with oxidative stress induced POAG-typical changes like ECM accumulation, cell death, disarrangement of the cytoskeleton, advanced senescence and the release of inflammatory markers. By pretreatment with antioxidants, prostaglandin analogues, beta-blockers or local carbonic anhydrase inhibitors, these effects were markedly reduced. In conclusion, oxidative stress is able to induce characteristic glaucomatous TM changes in vitro and these oxidative stress-induced TM changes can be minimised by the use of antioxidants and IOP-lowering substances. It is tempting to speculate that prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.

Ocular blood flow and visual field preservation?

Abstract Purpose The aetiology of primary open‐angle glaucoma (POAG) is almost certainly multifactorial. Elevated intraocular pressure (IOP) has been recognized as one of the most important risk factor for the progression of the glaucomatous damage. Nevertheless, other risk factors have been considered to be involved on the progression of the glaucomatous damage. Several population‐based studies have shown that low diastolic blood pressure and diastolic ocular perfusion pressure (OPP) are major risk factors for the genesis and progression of POAG. Additionally, there is increasing evidence that ocular ischemia is a primary and independent factor for the progression of the glaucomatous damage. Because OBF alterations are associated with the progression of the glaucomatous damage and dorzolamide seems to be capable of increasing OBF, it is conceivable that an increase of the OBF may protect against the glaucomatous visual field deterioration. Methods This hypothesis has been suggested by a recently paper published by our group, which has shown that dorzolamide 2% added to timolol 0.5%, each given twice daily, may prevent the visual field deterioration over the course of 4 years in individuals with primary open‐angle glaucoma (POAG). Finally, in a prospective, randomized, evaluator‐masked, and parallel study we compared the impact of dorzolamide and brinzolamide, each added to timolol, on the progression of the glaucomatous damage. The results of our study suggested that the patients treated with dorzolamide/timolol had half of the progression risk of patients treated with brinzolamide/timolol. Commercial interest

Effects of Oxidative Stress in Trabecular Meshwork Cells Are Reduced by Prostaglandin Analogues

The trabecular meshwork (TM) of glaucomatous eyes is characterized by cell loss, increased accumulation of extracellular matrix (ECM), and cellular senescence. One factor increasingly discussed in the pathogenesis of primary open-angle glaucoma (POAG) is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these typical glaucomatous changes in vitro and whether these oxidative stress-induced TM changes can be reduced by the application of prostaglandin analogues. Cultured human TM cells were exposed to 200 to 800 microM hydrogen peroxide (H(2)O(2)) for 1 hour. Cell loss was detected by cell-viability assay. Levels of fibronectin and MMP-2 mRNA were determined by real-time PCR analysis. Senescence-associated beta-galactosidase (SA-beta-Gal) activity was investigated by histochemical staining. The effects of prostaglandin analogues and benzalkonium chloride (BAC) on these glaucoma typical TM changes were investigated by preincubation of nonstressed or H(2)O(2)-treated cells with 1:100 diluted commercial solutions of bimatoprost, travoprost, and latanoprost or their corresponding BAC concentrations. H(2)O(2) induced cell death and fibronectin mRNA expression, but decreased the amount of MMP-2 mRNA. H(2)O(2) increased SA-beta-Gal activity. Additional pretreatment with BAC further increased the typical glaucomatous TM changes in vitro. These effects were reduced by preincubation with prostaglandin analogues in H(2)O(2)-treated and, to a lesser extent, in nonstressed cells. No reduction occurred in the presence of prostaglandin F receptor antagonists in H(2)O(2)-treated cells. Oxidative stress is able to induce characteristic glaucomatous TM changes in vitro, and these oxidative stress-induced TM changes can be minimized by the use of prostaglandin analogues. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.

Mitochondrial Complex I Defect Induces ROS Release and Degeneration in Trabecular Meshwork Cells of POAG Patients: Protection by Antioxidants

There is growing evidence that oxidative stress contributes to the progression of primary open-angle glaucoma (POAG), a leading cause of irreversible blindness worldwide. The authors provide evidence that mitochondrial dysfunction is a possible mechanism for the loss of trabecular meshwork (TM) cells in persons with POAG. TM from patients with POAG (GTM) and age-matched subjects without disease (NTM) were obtained by standard surgical trabeculectomy. Primary TM cultures were treated with one of the following mitochondrial respiratory chain inhibitors: rotenone (ROT, complex I inhibitor), thenoyltrifluoroacetone (TTFA, complex II inhibitor), myxothiazol or antimycin A (MYX, AM-complex III inhibitors); mitochondrial permeability transition (MPT) inhibitor cyclosporine A (CsA); and antioxidants vitamin E (Vit E) or N-acetylcysteine (NAC). Mitochondrial function was determined by changes in mitochondrial membrane potential (DeltaPsim) and adenosine triphosphate (ATP) production with the fluorescent probes 5,5',6,6'-tetrachloro-1,1'3,3'-tetraethylbenzimid azolocarbocyanine iodide (JC-1) and a luciferin/luciferase-based ATP assay, respectively. Reactive oxygen species (ROS) level, determined by H(2)-DCF-DA, and cell death, measured by lactate dehydrogenase activity and Annexin V-FITC labeling, were also examined. GTM cells have higher endogenous ROS levels, lower ATP levels, and decreased Delta Psi m and they are more sensitive to mitochondrial complex I inhibition than their normal counterparts. ROT induces a further increase in ROS production, the release of cytochrome c, and decreases in ATP level and Delta Psi m in GTM cells, eventually leading to apoptosis. Complex II and III inhibition had little effect on the cells. Antioxidants protect against ROT-induced death by inhibiting ROS generation and cytochrome c release. The authors propose that a mitochondrial complex I defect is associated with the degeneration of TM cells in patients with POAG, and antioxidants and MPT inhibitors can reduce the progression of this condition.

Les facteurs de risque du glaucome primitif à angle ouvert

To review the literature for risk factors involved in primary open-angle glaucoma (POAG). Articles and reviews studying the epidemiology and assessment of risk factors in POAG were collected from PubMed. The literature findings were divided into three categories: (1) What are the risks of developing POAG in healthy subjects? Significant factors include advancing age, family history of glaucoma, African origin, and elevated intraocular pressure; (2) What are the risks of developing POAG in ocular hypertensive patients? Significant factors include age, family history of glaucoma, reduced central corneal thickness, pronounced elevated IOP, and IOP fluctuations; and (3) What are the risks for progression in known cases of POAG? Significant factors include advancing age, elevated IOP fluctuations, IOP, elevated cup-over-disk ratio, disc asymmetry, and disk hemorrhages. A working knowledge of the risk factors for developing POAG and disease progression is essential to good clinical practice. Therefore, one could ideally concentrate resources on populations at risk for developing the disease as well as more actively treat those patients at risk for progression.

Risk factors for primary open angle glaucoma progression: what we know and what we need to know

Recent literature is reviewed in order to identify possible risk factors leading to primary open angle glaucoma progression and blindness. Several risk factors have been suggested to be important for progression of open angle glaucoma. Intraocular pressure appears to be an important risk factor for progression of glaucoma. It is still not clear if intraocular pressure fluctuation and central corneal thickness are related to progression. Myopia might be related to glaucoma progression as well as optic disc hemorrhages. Vascular factors appear to be related to progression also. Genetics seem to play an important role in open angle glaucoma. Identifying risk factors associated with progression of patients with primary open angle glaucoma is essential to our clinical practices. The level of understanding regarding those risks is suboptimal at this point. Prospective long-term studies are needed if we wish to better understand the disease and help those patients at greater risk of progression and blindness.

Oxidative stress in the trabecular meshwork – Preventive effects of Prostaglandin analogues

Abstract Purpose: The trabecular meshwork (TM) of primary open angle glaucoma (POAG) is characterized by an increased accumulation of extracellular matrix, cellular senescence, and the loss of TM cells. One factor in the pathogenesis of POAG is oxidative stress. The goal of this study was to determine whether oxidative stress is able to trigger these POAG specific changes in cultured human TM cells and whether these changes could be reduced or prevented by the application of prostaglandin analogues (PA). Methods: Cultured human TM cells were stressed with hydrogen peroxide (H2O2) for 1 hour. Levels of fibronectin and MMP‐9 mRNA were analyzed by RT‐PCR. Senescence‐associated beta‐galactosidase (SA‐ß‐gal) activity was detected by histochemical staining. Cell loss was investigated by live dead assay. The effects of PA and benzalkonium chloride (BAC) on POAG typical TM changes were investigated by pre‐incubation with solutions of bimatoprost, travoprost and latanprost or its corresponding BAC concentrations of the either non stimulated or H2O2‐treated cells. Results: H202 markedly influenced the mRNA expression of fibronectin (1.8 fold), MMP‐9 (0.4 fold) and increased SA‐ß‐gal activity to 12 fold. Incubation with 600 μM H2O2 for induced 50% of dead cells. Pretreatment with BAC alone induced POAG typical TM changes in non‐stimulated and H2O2‐treated cells. These effects were reduced by preincubation with PA in H2O2‐treated cells and to a lesser extent in non stimulated cells. Conclusions: Oxidative stress is able to induce several characteristic POAG TM changes in vitro and these oxidative stress‐induced TM changes can be minimized by the use of PA. Thus, prevention of oxidative stress exposure to the TM may help to reduce the progression of POAG.

How Might Corneal Elasticity Help Us Understand Diabetes and Intraocular Pressure?

To determine how changes in corneal elasticity/stiffness might influence intraocular pressure (IOP) readings in diabetic patients. A systematic review of the literature was performed to understand the conflicting relationship between diabetes, elevated IOP, and glaucoma progression. Diabetic patients have been found to have statistically significant higher IOP readings in some population-based studies compared to non-diabetics. Insulin resistance states, hyperglycemia and glycosylated hemoglobin have been correlated with higher IOP (1 mmHg) measurements in diabetic patients. In the Ocular Hypertension Treatment Study (OHTS), a self reported history of diabetes was found to be protective against the progression of primary open-angle glaucoma. Small differences in IOP measurements in diabetic patients may be due to corneal stiffening, as demonstrated by the protective effect of glucose-mediated collagen cross-linking against the manifestation and keratometric progression of keratoconus. Different collagen cross-linking agents may induce different degrees of corneal stiffening, which can result in differences in measured IOP. Glucose-mediated corneal stiffening due to collagen cross-linking might be responsible for IOP overestimation in diabetic patients. Corneal stiffening might explain why diabetic eyes tend to have higher IOP readings in large population-based studies and why those with ocular hypertension have a reduced risk for glaucoma progression.

Association of E-Cadherin Gene 3’-UTR C/T Polymorphism with Primary Open Angle Glaucoma

Purpose: E-cadherin (E-CDH) is one of the most important cell surface glycoproteins involved in cell morphogenesis. In primary open angle glaucoma (POAG), the extracellular matrixes of trabecular meshwork and lamina cribrosa in the optic nerve head are out of balance. We suspected that E-CDH by way of metalloproteinases is closely related to POAG. We therefore investigated the relationship between CDH-1 gene 3′ untranslated region (3′-UTR) polymorphism and POAG patients in order to support this hypothesis. Patients and Methods: We enrolled 60 POAG patients and 103 healthy volunteers from the Department of Ophthalmology at the China Medical University Hospital, Taichung, Taiwain, ROC. None of the control subjects had a history of eye disease and all underwent the same examination as the POAG patients. PCR-based analysis of the restriction fragment length polymorphism was used to test the CDH-1 gene 3′-UTR polymorphism. All statistical analyses were performed by the χ² test. Result: There was a significant difference in the distribution of the CDH-1 gene 3′-UTR C/T polymorphism between POAG patients and the normal controls (p <0.000). The odds ratio of the ‘C’ allele was al so significantly different between both groups (odds ratio = 5.510, 95% confidence interval = 3.171–9.574). Conclusion: CDH-1 is closely related to metalloproteinase and plays an important but not well-understood role in the onset and progression of POAG. The exact role of CDH-1 in POAG could be resolved by the posttranslated products of the gene and the protein-protein interaction of the gene products in the future.

Effects of travoprost 0.004% ophthalmic solution, six weeks after its laminated packaging had been removed, in primary open-angle glaucoma: A randomized, controlled, investigator-blinded study

Background: Primary open-angle glaucoma (POAG) is a chronic and progressive optic nerve and retinal nerve fiber layer neuropathy, with characteristic visual field damage. The intraocular pressure (IOP) is typically higher than the level considered statistically normal. Although there is no known cure, appropriate reduction of IOP with hypotensive drugs (eg, the topical prostaglandin analogue travoprost) delays the progression of POAG. Chemical-stability studies of travoprost performed by the manufacturer suggest that the stability of travoprost is maintained beyond the expiration date, which is 6 weeks after the laminated packaging has been opened. Objective: The goal of this study was to assess the efficacy and tolerability of travoprost 0.004% ophthalmic solution, 6 to 12 weeks after its expiration date, in patients with POAG. Methods: This randomized, controlled, investigator-blinded study was conducted at 2 centers in Brazil: the Ophthalmology Department, Federal University of Goi s, Goi nia, and the Ophthalmology Department, Santa Casa de Misericordia Hospital in S o Jos do Rio Preto, Sao Paulo. Patients with POAG (in 1 or both eyes) were randomly assigned to receive travoprost, either from a bottle from which the laminated packaging had been removed and that had been stored at room light and temperature for 6 weeks (ie, after the expiration date; opened group), or from a bottle that had been sealed until first use by the patient (control group). Drug was to be administered, 1 drop in the lower conjunctival sac (in the affected eye[s]), QD between 7 pm and 9 pm, for 6 weeks. IOP was measured at study weeks 0 (baseline), 4, and 6. The 2 treatment groups were compared with regard to hypotensor effect and incidence of adverse events (AEs). Results: Thirty-one patients completed the study (55 eyes; 28 right and 27 left eyes; 35 eyes of women, 20 eyes of men). The mean (SD) ages of the opened and control groups were 61.8 (13.5) and 62.8 (14.1) years, respectively. Twenty-four patients were included in both treatment groups (ie, 1 eye per group). The baseline IOP was similar between the 2 treatment groups. There was a significant reduction in IOP in both groups at 4 and 6 weeks (both, P < 0.001 vs baseline). However, no significant differences in IOP were found between the 2 treatment groups at any time during the study. Conjunctive hyperemia and a burning sensation in the eye immediately after application were the only AEs reported; the incidence of these was similar between the 2 treatment groups. Conclusions: In this study of patients with POAG, IOPs and AEs were similar in eyes receiving 6 weeks of treatment with travoprost 0.004% ophthalmic solution, either from bottles from which the laminated packaging had been opened and that had been stored at room light and temperature for 6 weeks (ie, after the expiration date), or from bottles that had been sealed until first use by the patient. These results suggest that travoprost remains effective for at least 12 weeks after the laminated packaging has been opened.

Medical Outcomes of Glaucoma Therapy from a Nationwide Representative Survey

To evaluate the medical outcomes of patients treated for primary open angle glaucoma (POAG) or ocular hypertension. Sixty-eight ophthalmologists selected at random from a national professional list in France were asked to report on disease progression in consecutive patients who they saw in their clinics and who had either POAG, normal tension glaucoma/ocular hypertension, and who were aged >18 years of age. Data on sociodemographics, general and ocular comorbidities, glaucoma risk factors, visual acuity (VA), optic nerve head (ONH) clinical data, and visual fields were collected. Disease progression was defined as a deterioration of ONH and/or visual field since initial diagnosis. Changes in treatment were also monitored. A treatment change was defined as adding a new drug or changing any of the current treatments. Time to treatment failure was compared using the Wilcoxon test applied to survival curves. Of 127 patients who were evaluated, 12 developed a disease progression after diagnosis (average follow-up 2.4 years). No statistically significant difference in the known confounding factors of disease progression was found between patients with or without disease progression. At 32 months, 2.6% of the patients with no changes in treatment had a DP, compared with 22.6% with one change in treatment and 46.2% with two or more changes in treatment (p < 0.03). Patients who experienced adverse effects (p < 0.008) and those who said they were unhappy with their treatment (p < 0.03) more often experienced disease progression. An estimated 9.4% of a representative sample of patients with POAG or ocular hypertension experienced disease progression within 2.5 years of initial diagnosis. Patients with disease progression had more changes in treatment and adverse events; they were also more likely to have complained about being unhappy with their treatment.

Higher Concentration of Transforming Growth Factor- β in Aqueous Humor of Glaucomatous Eyes and Diabetic Eyes

Purpose: Diabetic retinopathy and glaucoma are the primary causes of acquired blindness. Cytokines including transforming growth factor (TGF)-β may be involved in these diseases. We therefore collected aqueous humor samples from patients with glaucoma and/or diabetes who were undergoing surgery, and determined the concentration of TGF-β. Methods: Aqueous humor samples were collected from 80 patients (84 eyes), including 19 eyes with primary open-angle glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated with POAG. Twenty-five eyes with cataract served as controls. The concentration of TGF-β1 or TGF-β2 was measured by enzyme-linked immunosorbent assay. Results: The concentration of TGF-β1 was less than 0.1 pg/mL in all of the groups. In contrast to controls who had 1001.4 ± 444.1 pg/mL, the concentration of total TGF-β2 in the diabetes group was 1715.6 ± 882.1 pg/mL, and that in the diabetes complicated with POAG group was 1692.9 ± 361.9 pg/mL. These were significantly higher than that in controls. In contrast to the controls who had 321.2 ± 197.9 pg/mL, the concentration of mature TGF-β2 with POAG was 822.5 ± 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 ± 648.4 pg/mL. These were significantly higher than that in the controls. The eyes with diabetes complicated with POAG also had a significantly higher concentration than the eyes with diabetes alone. Conclusion: Total TGF-β2 and mature TGF-β2 in high concentration may correlate with progression of POAG, diabetes, and diabetes complicated with POAG.