Low-pressure Glaucoma Treatment Study Research Articles

Comparing Five Criteria for Evaluating Glaucomatous Visual Fields

No consensus exists on the relative superiority among criteria for evaluating glaucomatous visual field (VF) damage. We compared the sensitivities and specificities of 5 criteria-Glaucoma Hemifield Test (GHT), Hoddap-Anderson-Parrish 2 (HAP2), Foster, United Kingdom Glaucoma Treatment Study (UKGTS), and Low-pressure Glaucoma Treatment Study (LoGTS)-across various levels of functional and structural glaucomatous damage. Retrospective cross-sectional study. This single-center study included patients with suspect or known glaucoma with reliable VF (Humphrey 24-2 Swedish Interactive Thresholding Algorithm) and optical coherence tomography (OCT; Spectralis, Heidelberg Engineering) examinations within a 4-month period. One eye per patient was included. The level of functional and structural damage was defined by mean deviation (MD) and by an OCT score, respectively. We created the OCT score by counting the number of abnormal (MD percentile [P] <1%) global and sectoral averages of optic nerve head MRW, circumpapillary RNFL thickness, and macular GCL thickness. We inferred specificities and sensitivities from positive rates of the criteria in patients with low glaucomatous damage (MD at P ≥ 10% or OCT score = 0) and with higher damage (MD at P < 10% or OCT score > 0), respectively. We included 1230 patients. In patients with low glaucomatous damage, HAP2 and UKGTS had higher positive rates, suggesting lower specificities, whereas GHT, Foster, and LoGTS had lower positive rates, suggesting higher specificities. In patients with higher glaucomatous damage, HAP2 and UKGTS had higher positive rates, indicating higher sensitivities, whereas GHT, Foster, and LoGTS had lower positive rates, indicating lower sensitivities. No criteria had uniformly superior performance. Selection of criteria should consider the degree of damage anticipated and the desire for either higher sensitivity or specificity.

Normal-tension Glaucoma Management: A Survey of Glaucoma Sub-specialists in Korea

PurposeTo investigate the current management patterns of glaucoma subspecialists with regard to normal-tension glaucoma (NTG) in Korea and to determine the effect of the two largest NTG trials on their clinical practice.MethodsA questionnaire survey was sent to glaucoma subspecialist members of the Korean Glaucoma Society. The questionnaire concerned regular practice with respect to NTG and the extent to which it has been influenced by the Collaborative Normal-tension Glaucoma Study and the Low-pressure Glaucoma Treatment Study (LoGTS).ResultsA total of 134 glaucoma subspecialists completed the survey, with a response rate of 56%. The survey reported that 88% and 78% of glaucoma subspecialists were familiar with the Collaborative Normal-tension Glaucoma Study and the LoGTS, respectively. With respect to mild or moderate NTG, most of the respondents (87%–91%) tended to treat their patients immediately without waiting for structural or functional progression. Among the respondents, 47 indicated that the LoGTS results—according to which, 20% of the respondents tended to use brimonidine more often—affected their management. The first-choice topical drugs for NTG were prostaglandin analogues (76%), brimonidine (9%), beta-blockers (8%), and topical carbonic anhydrase inhibitor (6%).ConclusionsRegarding mild-to-moderate NTG, Korean glaucoma subspecialists tended to initiate treatment without waiting for further progression. The impact of the LoGTS on NTG management was not dominant in clinical practice in Korea. Prostaglandin analogs are the most frequently selected first-choice drugs for the management of NTG in Korea.

Normal tension glaucoma management: a survey of contemporary practice

ObjectiveThe aim of this study was to investigate contemporary practice patterns with respect to normal tension glaucoma (NTG) management and to determine whether the 2 largest NTG trials have influenced ophthalmologists’ clinical practice. MethodsA survey questionnaire was sent to ophthalmologists via the American Glaucoma Society, the Canadian Glaucoma Society, and the Canadian Ophthalmological Society. The questionnaire was designed to investigate ophthalmologists’ usual practice with respect to NTG and the extent to which practice has been influenced by the Collaborative Normal Tension Glaucoma Study (CNTGS) and the Low pressure Glaucoma Treatment Study (LoGTS). ResultsIn total, 419 ophthalmologists completed the survey. Of these, 264 respondents were glaucoma subspecialists. The survey showed that 95% and 64% of ophthalmologists were familiar with the CNTGS and the LoGTS, respectively. Of the respondents, 70% indicated that they would initiate treatment in mild-to-moderate NTG without waiting for documented disease progression. Of the respondents, 61% of the total surveyed and 50% of the glaucoma subspecialists felt that the LoGTS results had no impact on their usual clinical practice. The first-choice topical drug for NTG was a prostaglandin analogue (88% of respondents) or brimonidine (10% of respondents). ConclusionsMost ophthalmologists treat NTG more aggressively than recommended by the CTNGS protocol. Most ophthalmologists felt that the LoGTS results had no impact on their normal clinical practice. The prostaglandin analogues are, by far, the most popular choice of drug for contemporary management of NTG.

Neuroprotection for treatment of glaucoma in adults.

Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide.Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death. The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016. We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG.Minimum follow-up time was four years. Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until study investigators provide additional study details. We documented reasons for excluding studies from the review. We included one multicenter RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was progression of visual field loss after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, the investigators excluded 12 (6.3%) after randomization; 77 participants (40.5%) did not complete four years of follow-up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%).Of those remaining in the study at four years, participants assigned to brimonidine showed less progression of visual field loss than participants assigned to timolol (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.14 to 0.86; 101 participants). Because of high risk of attrition bias and potential selective outcome reporting, we graded the certainty of evidence for this outcome as very low. At the four-year follow-up, the mean IOP was similar in both groups among those for whom data were available (mean difference 0.20 mmHg, 95% CI -0.73 to 1.13; 91 participants; very low-certainty evidence). The study authors did not report analyzable data for visual acuity or any data related to vertical cup-disc ratio, quality of life, or economic outcomes. The most frequent adverse event was ocular allergy to the study drug, which affected more participants in the brimonidine group than the timolol group (RR 5.32, 95% CI 1.64 to 17.26; 178 participants; very low-certainty evidence). Although the only trial we included in this review found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that we can draw no conclusions from this finding.Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG. Such research should focus on outcomes important to patients, such as preservation of vision, and how these outcomes relate to cell death and optic nerve damage. As OAG is a chronic, progressive disease with variability in symptoms, RCTs designed to measure the effectiveness of neuroprotective agents require a long-term follow-up of five years or longer to detect clinically meaningful effects.

Risk Factors for Optic Disc Hemorrhage in the Low-Pressure Glaucoma Treatment Study

To investigate risk factors for disc hemorrhage detection in the Low-Pressure Glaucoma Treatment Study. Cohort of a randomized, double-masked, multicenter clinical trial. Low-Pressure Glaucoma Treatment Study patients with at least 16months of follow-up were included. Exclusion criteria included untreated intraocular pressure (IOP) of more than 21mm Hg, visual field mean deviation worse than-16 dB, or contraindications to study medications. Patients were randomized to topical treatment with timolol 0.5% or brimonidine 0.2%. Stereophotographs were reviewed independently by 2 masked graders searching for disc hemorrhages. The main outcomes investigated were the detection of disc hemorrhage at any time during follow-up and their recurrence. Ocular and systemic risk factors for disc hemorrhage detection were analyzed using the Cox proportional hazards model and were tested further for independence in a multivariate model. Two hundred fifty-three eyes of 127 subjects (mean age, 64.7 ± 10.9 years; women, 58%; European ancestry, 71%) followed up for an average ± standard deviation of 40.6 ± 12months were included. In the multivariate analysis, history of migraine (hazard ratio [HR], 5.737; P= .012), narrower neuroretinal rim width at baseline (HR, 2.91; P= .048), use of systemic β-blockers (HR, 5.585; P= .036), low mean systolic blood pressure (HR, 1.06; P= .02), and low mean arterial ocular perfusion pressure during follow-up (HR, 1.172; P= .007) were significant and independent risk factors for disc hemorrhage detection. Treatment randomization was not associated with either the occurrence or recurrence of disc hemorrhages. In this cohort of Low-Pressure Glaucoma Treatment Study patients, migraine, baseline narrower neuroretinal rim width, low systolic blood pressure and mean arterial ocular perfusion pressure, and use of systemic β-blockers were risk factors for disc hemorrhage detection. Randomization assignment did not influence the frequency of disc hemorrhage detection.

Why the Low-Pressure Glaucoma Treatment Study makes sense

“While the frequency of disc hemorrhange in the Low-Pressure Glaucoma Treatment Study was not reported, we suspect the study is enriched with patients who demonstrated retinal vascular dysregulation and that brimonidine use favorably altered the retinal hemodynamic profile in a manner that translated into less visual field loss when compared with the timolol-treated group.” Expert Review of Ophthalmology

Risk Factors for Visual Field Progression in the Low-pressure Glaucoma Treatment Study

To investigate risk factors associated with visual field progression in the Low-pressure Glaucoma Treatment Study, a prospective trial designed to compare the effects of the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% on visual function in low-pressure glaucoma. Prospective cohort study. Low-pressure Glaucoma Treatment Study patients with ≥5 visual field tests during follow-up were included. Progression was determined using pointwise linear regression analysis, defined as the same 3 or more visual field locations with a slope more negative than -1.0 dB/year at P < 5%, on 3 consecutive tests. Ocular and systemic risk factors were analyzed using Cox proportional hazards model and further tested for independence in a multivariate model. A total of 253 eyes of 127 subjects (mean age, 64.7 ± 10.9 years; mean follow-up, 40.6 ± 12 months) were analyzed. Eyes randomized to timolol progressed faster than those randomized to brimonidine (mean rates of progression, -0.38 ± 0.9 vs 0.02 ± 0.7 dB/y, P < .01). In the final multivariate model adjusting for all tested covariates, older age (hazard ratio [HR] = 1.41/decade older, 95% confidence interval [CI] = 1.05 to 1.90, P = .022), use of systemic antihypertensives (HR = 2.53, 95% CI = 1.32 to 4.87, P = .005), and mean ocular perfusion pressure (HR = 1.21/mm Hg lower, 95% CI = 1.12 to 1.31, P < .001) were associated with progression whereas randomization to brimonidine revealed a protective effect (HR = 0.26, 95% CI = 0.12 to 0.55, P < .001). While randomization to brimonidine 0.2% was protective compared to timolol 0.5%, lower mean ocular perfusion pressure increased the risk for reaching a progression outcome in the Low-pressure Glaucoma Treatment Study. This suggests that the beneficial effect of randomization to the brimonidine arm was independent of possible differences in ocular perfusion pressures between the 2 treatment arms. The current results and large number of drop-outs in the brimonidine 0.2% arm suggest that more research is necessary before altering clinical practice paradigms.

Recent clinical pearls from clinical trials in glaucoma

Over the past several years, numerous clinical trials in glaucoma have contributed to our understanding of the medical and surgical treatment of the disease. The goal of this review is to summarize the findings and conclusions of what the authors feel are the key clinical trials in glaucoma. One of the major findings of Low-Pressure Glaucoma Treatment study was that patients randomized to the brimonidine group were statistically less likely to have progressive visual field loss than those randomized to the timolol group, even though there was no significant difference between the intraocular pressure (IOP)-lowering effect of these two drugs. The Ocular Hypertension Treatment Study has effectively demonstrated that patients with ocular hypertension should be risk stratified prior to initiation of treatment and that it appears to be relatively safe to delay treatment in low-risk patients. The 3-year canaloplasty study demonstrates the long-term safety and efficacy of this surgery. However, it also demonstrates that canaloplasty can deliver a modest IOP reduction and therefore is likely more suited for patients with mild damage and a higher target IOP. The 1-year results from the Ahmed Baerveldt Comparison Study do not demonstrate a clear superiority of one implant over the other. These findings are consistent with prior retrospective studies in the literature. These four studies have furthered our understanding of the field of glaucoma and provided key insights into the medical and surgical management of patients with this complex disease.

A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

A Randomized Trial of Brimonidine Versus Timolol in Preserving Visual Function: Results From the Low-pressure Glaucoma Treatment Study

To compare the alpha2-adrenergic agonist brimonidine tartrate 0.2% to the beta-adrenergic antagonist timolol maleate 0.5% in preserving visual function in low-pressure glaucoma. Randomized, double-masked, multicenter clinical trial. Exclusion criteria included untreated intraocular pressure (IOP) >21 mm Hg, visual field mean deviation worse than -16 decibels, or contraindications to study medications. Both eyes received twice-daily monotherapy randomized in blocks of 7 (4 brimonidine to 3 timolol). Standard automated perimetry and tonometry were performed at 4-month intervals. Main outcome measure was field progression in either eye, defined as the same 3 or more points with a negative slope ≥-1 dB/year at P<5%, on 3 consecutive tests, assessed by pointwise linear regression. Secondary outcome measures were progression based on glaucoma change probability maps (GCPM) of pattern deviation and the 3-omitting method for pointwise linear regression. Ninety-nine patients were randomized to brimonidine and 79 to timolol. Mean (± SE) months of follow-up for all patients was 30.0 ± 2. Statistically fewer brimonidine-treated patients (9, 9.1%) had visual field progression by pointwise linear regression than timolol-treated patients (31, 39.2%, log-rank 12.4, P=.001). Mean treated IOP was similar for brimonidine- and timolol-treated patients at all time points. More brimonidine-treated (28, 28.3%) than timolol-treated (9, 11.4%) patients discontinued study participation because of drug-related adverse events (P=.008). Similar differences in progression were observed when analyzed by GCPM and the 3-omitting method. Low-pressure glaucoma patients treated with brimonidine 0.2% who do not develop ocular allergy are less likely to have field progression than patients treated with timolol 0.5%.

Is brimonidine better at stabilizing visual field than timolol?

Abstract Purpose Alpha‐2 adrenergic agonists are neuroprotective in animal models of focal cerebral ischemia. Brimonidine protects the retinal ganglion cell (RGC) from secondary degeneration following partial crush injury to the rat optic nerve and in an ocular hypertensive rat model. The mechanism for this effect is up‐regulation of brain‐derived neurotrophic factor in RGC and the retina. Brimonidine activates the alpha‐2 adrenoceptor at 2 nM. Topical administration of brimonidine produces pharmacologic drug concentrations in the vitreous (100‐170 nM) in humans that provides a drug delivery route to the RGCs sufficient to bind and activate the alpha‐2 adrenoceptor. In this way, brimonidine could function to maintain the health of the optic nerve independent of its ability to reduce intraocular pressure (IOP) Methods The Low‐pressure Glaucoma Treatment Study (LoGTS) is a triple masked, randomized, multicenter clinical trial of the efficacy of monotherapy with brimonidine versus timolol eye drops to alter the course of low‐pressure (normal‐tension) glaucoma (untreated IOP &lt; 22 mmHg). The primary outcome was visual field progression analyzed using point‐wise linear regression analysis. This methodology required a minimum of four visual fields to obtain and compared the slope of decibel sensitivity of each test location to all previous examinations. Field progression was defined as a negative slope &gt; 1.0 decibel/year with a significance P£0.05 for the same three or more test locations on three consecutive examinations (i.e., over an 8 month interval). Results Previously published articles contains a detailed description of the study methods and baseline patient characteristics and baseline visual field and IOP asymmetry. The current presentation will discuss LoGTS outcomes. Commercial interest

A clinical trial studying neuroprotection in low-pressure glaucoma

The Low-Pressure Glaucoma Treatment Study is a double-masked, randomized trial comparing the visual outcomes of 190 low-pressure glaucoma patients randomized to intraocular pressure reduction with brimonidine tartrate or timolol maleate. Baseline characteristics of participants are compared to published studies.

Special considerations in low-tension glaucoma

Low-pressure (low-tension) glaucoma is reviewed in relation to neuroprotection, that is, the therapeutic strategy to keep neurons living and functionally connected to targets within the brain. Baseline results of the Low-Pressure Glaucoma Treatment Study (LoGTS) are reviewed.

Visual Field and Intraocular Pressure Asymmetry in the Low-Pressure Glaucoma Treatment Study

To explore the relationship between asymmetric baseline intraocular pressure (IOP) and asymmetric visual field (VF) loss in the Low-Pressure Glaucoma Treatment Study. Randomized, multicenter, controlled clinical trial. Low-pressure glaucoma (LPG) patients 30 years or older were identified. Exclusion criteria included an untreated pressure > 21 mmHg, advanced VF loss, and contraindications to study medications. A baseline VF was created using the average of 2 reliable Humphrey full-threshold examinations. A baseline diurnal IOP curve was performed without IOP-lowering medication. Mean diurnal, peak, trough, IOP range (peak - trough), and standard deviation (SD) of IOP measurements, and mean deviation (MD) and corrected pattern SD (CPSD) of VF examinations. One hundred ninety patients were enrolled (mean age, 64.9+/-10.7 years). Mean deviation and CPSD were not correlated with mean, peak, trough, or peak minus trough (P - T) IOP (Ps = 0.2-0.9). Among patients with unilateral VF loss (n = 53 [27.9%]), there were no differences (Ps = 0.3-0.9) in any IOP parameter between the normal VF eye and fellow glaucomatous eyes. Among patients with bilateral VF loss (n = 137 [72.1%]), mean, peak, trough, and P - T IOPs were similar in eyes with a better VF MD compared with eyes with a worse VF MD (Ps = 0.2-0.7). Cross-classified contingency tables demonstrated no relationship (Ps = 0.1-0.3) between IOP and VF MD or CPSD using chi-square analysis. Intraocular pressure asymmetry is unrelated to VF asymmetry in the Low-Pressure Glaucoma Treatment Study, suggesting an unclear pathogenic relationship between IOP and glaucomatous damage in eyes with LPG.

The Low-pressure Glaucoma Treatment Study (LoGTS): Study design and baseline characteristics of enrolled patients

The Low-Pressure Glaucoma Treatment Study (LoGTS) seeks to evaluate visual field stability in low-pressure glaucoma patients randomized to intraocular pressure reduction in both eyes with topical twice daily brimonidine tartrate 0.2% versus twice daily timolol maleate 0.5%. This article describes the LoGTS design and presents baseline characteristics of the subjects.Randomized, multicenter, double-masked clinical trial.Low-pressure glaucoma patients 30 years of age or older were identified. Exclusion criteria included an untreated pressure of more than 21 mmHg, advanced visual field loss, and contraindications to study medications.Randomization of both eyes to double-masked monotherapy with brimonidine or timolol. Follow-up visits included Humphrey 24-2 full-threshold perimetry, tonometry every 4 months, and annual optic disc photography.Progression of visual field loss.One hundred ninety patients were randomized between 1998 and 2000. Mean age (+/-standard deviation) was 64.9+/-10.7 years. Women comprised 59.5% of the patients. Fifty-three patients (27.9%) had unilateral field loss. The 137 patients with bilateral field loss were older than those with unilateral field loss: 65.7 versus 62.3 years of age (P<0.05). Mean untreated diurnal intraocular pressures were similar between the eyes of the bilateral patients (mean, 15.5 mmHg in both eyes) and unilateral patients (mean, 16.0 mmHg in field loss vs. 15.6 mmHg in fellow eyes). Visual field mean deviation for all eyes was -5.4+/-4.7 decibels. Central corneal thickness in 168 phakic patients was 543 +/- 35 microm (range, 435-655 microm); thickness was less than 500 microm in 15 eyes and was more than 600 microm in 11 eyes. Mean vertical cup-to-disc ratio for all eyes was 0.67+/-0.15. Unilateral field loss patients had a larger cup-to-disc ratio in the field loss eye (0.75+/-0.12) than the fellow eye with a normal field (0.60+/-0.17, P<0.0001). Disc hemorrhage was present at baseline in 29 patients (32 eyes).The LoGTS was successfully able to recruit and enroll patients with open-angle glaucoma and statistically normal intraocular pressure into a longitudinal, prospective clinical trial comparing 2 different glaucoma medications. Baseline characteristics of note were a preponderance of females, unilateral field loss in 27.9% of participants, and frequent optic disc hemorrhage. Central corneal thickness had a normal distribution and did not account for false low-pressure measurements in LoGTS patients.