The Glaucoma Intensive Treatment Study (GITS): a randomized controlled trial comparing intensive and standard treatment on 5 years visual field development.

PURPOSE: To assess the effect of an intensive initial IOP lowering treatment strategy on the progression of visual field damage. DESIGN: A randomized, controlled, open-labelled two-center clinical trial. METHODS: A total of 242 patients with newly detected early or moderate untreated open-angle glaucoma were enrolled at two university hospitals in Sweden. Participants were randomly allocated (1:1) to either initial treatment with intensive IOP-lowering medications followed by 360° laser trabeculoplasty (LTP), or to traditional mono-therapy, which was increased when deemed necessary. The primary study outcome of interest was the predicted remaining visual field, as measured by the visual field index (VFI) at projected end of life. RESULTS: The median untreated IOP was 24 mmHg in both treatment groups. During follow-up, median and mode IOP was 17 mmHg in the mono- and 14 mmHg in the multi-treated group. In the mono-treated group the median VFI at projected end of life was 79.3%, and in the multi-treated group 87.1%, p=0.15. Annual rate of progression of visual field damage was faster in mono-treated than in multi-treated participants; median losses per year were 0.65 and 0.25 percentage units respectively, p=0.09. Progression events occurred in 21% of the mono- and in 11% of the multi-treated participants, p=0.03. Adverse events, mostly mild, were reported in 25% of the mono-, and in 36% of the multi-treated participants. Differences in visual field outcomes between treatment groups were more pronounced in participants having higher baseline IOP defined by median split of untreated IOP values. CONCLUSION: In the overall analysis the visual field outcomes were not overwhelming better in the multi-treated group, but post-hoc analysis showed definite benefit in patients with higher untreated IOP. Based upon the results of this study, initial intensive treatment may be considered in glaucoma patients with high untreated IOP at diagnosis, while we found no evidence that multi-therapy should be given routinely to all glaucoma patients.

Long-term follow-up of laser trabeculoplasty in multi-treated glaucoma patients.

PURPOSE: To evaluate the long-term effect of laser trabeculoplasty (LTP) in patients randomized to multi-treatment in the Glaucoma Intensive Treatment Study (GITS). METHODS: Patients with untreated newly diagnosed open-angle glaucoma were treated with three intraocular pressure (IOP)-lowering substances for 1 week and then 360° argon or selective LTP was performed. IOP was measured just before LTP and repeatedly during the 60-month study period. Our previous report on 12 months follow-up data revealed no effect of LTP in eyes having an IOP <15 mmHg before the laser treatment. RESULTS: Before LTP, the mean IOP ± standard deviation in all 152 study-eyes of 122 multi-treated patients was 14.0 ± 3.5 mmHg. Three eyes of three deceased patients were lost to follow-up during the 60 months. After exclusion of eyes that received increased therapy during follow-up, the IOP was significantly reduced at all visits up to 48 months in eyes with pre-LTP IOP ≥15 mmHg; 2.6 ± 3.1 mmHg at 1 month and 1.7 ± 2.8 mmHg at 48 months, n = 56 and 48, respectively. No significant IOP reduction was seen in eyes with pre-LTP IOP <15 mmHg. Seven eyes, i.e., <13%, with pre-LTP IOP ≥15 mmHg at baseline had required increased IOP-lowering therapy at 48 months. CONCLUSION: LTP performed in multi-treated patients may provide a useful IOP reduction that is maintained over several years. This was true on a group level when the initial IOP was ≥15 mmHg, but if the pre-laser IOP was lower than that, chances of LTP success were small.

Threat to fixation and vision-related quality of life in early open-angle glaucoma - results from the Glaucoma Intensive Treatment Study.

PURPOSE: To determine the effect of glaucomatous visual field (VF) damage close to the point of fixation, called threat-to-fixation (TTF), on vision-related quality of life (VRQoL) in open-angle glaucoma. METHODS: A total of 239 patients from the Glaucoma Intensive Treatment Study (GITS) were included in this analysis. The second VF of patients with newly diagnosed primarily early glaucoma was evaluated for the presence or absence of TTF. TTF was defined as VF loss including one or more of the four innermost test points depressed at p < 1% in the total deviation probability map of Humphrey 24-2 SITA Standard visual fields. VRQoL was evaluated using Rasch-analysed National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) scores. The correlation between VRQoL and TTF was evaluated using uni- and multivariable regression analyses. RESULTS: TTF was present in at least one eye in 115 patients (48%); located in the superior hemifield alone in 47% (54 of 115), in the inferior hemifield alone in 23% (27 of 115), and in 30% (34 of 115) in both hemifields. The median Rasch-calibrated NEI VFQ-25 scores were identical when comparing patients with TTF (VRQoL score 66, 95% CI: 23-100) and those with no-TTF (VRQoL score 66, 95% CI: 21-100) (p = 0.925). Neither the presence of TTF (R2  = -0.004, p = 0.968) nor the location of TTF (R2  = 0.023, p = 0.103) was significantly correlated to Rasch-calibrated NEI VFQ-25 scores. CONCLUSION: The presence of TTF did not influence VRQoL, as measured by the NEI-VFQ-25, in this relatively large group of patients with mainly early glaucoma.

Estimating the Length of the Preclinical Detectable Phase for Open-Angle Glaucoma.

Importance: A 50% reduction of glaucoma-related blindness has previously been demonstrated in a population that was screened for open-angle glaucoma. Ongoing screening trials of high-risk populations and forthcoming low-cost screening methods suggest that such screening may become more common in the future. One would then need to estimate a key component of the natural history of chronic disease, the mean preclinical detectable phase (PCDP). Knowledge of the PCDP is essential for the planning and early evaluation of screening programs and has been estimated for several types of cancer that are screened for. Objective: To estimate the mean PCDP for open-angle glaucoma. Design, Setting, and Participants: A large population-based screening for open-angle glaucoma was conducted from October 1992 to January 1997 in Malmö, Sweden, including 32 918 participants aged 57 to 77 years. A retrospective medical record review was conducted to assess the prevalence of newly detected cases at the screening, incidence of new cases after the screening, and the expected clinical incidence, ie, the number of new glaucoma cases expected to be detected without a screening. The latter was derived from incident cases in the screened age cohorts before the screening started and from older cohorts not invited to the screening. A total of 2029 patients were included in the current study. Data were analyzed from March 2020 to October 2021. Main Outcomes and Measures: The length of the mean PCDP was calculated by 2 different methods: first, by dividing the prevalence of screen-detected glaucoma with the clinical incidence, assuming that the screening sensitivity was 100% and second, by using a Markov chain Monte Carlo (MCMC) model simulation that simultaneously derived both the length of the mean PCDP and the sensitivity of the screening. Results: Of 2029 included patients, 1352 (66.6%) were female. Of 1420 screened patients, the mean age at screening was 67.4 years (95% CI, 67.2-67.7). The mean length of the PCDP of the whole study population was 10.7 years (95% CI, 8.7-13.0) by the prevalence/incidence method and 10.1 years (95% credible interval, 8.9-11.2) by the MCMC method. Conclusions and Relevance: The mean PCDP was similar for both methods of analysis, approximately 10 years. A mean PCDP of 10 years found in the current study allows for screening with reasonably long intervals, eg, 5 years.

The glaucoma intensive treatment study: interim results from an ongoing longitudinal randomized clinical trial.

PURPOSE: The aim of the study was to determine the perimetric rate of glaucoma progression in the ongoing Glaucoma Intensive Treatment Study (GITS) after 3 years of follow-up. DESIGN: This is a randomized, two-centre, prospective open-labelled treatment trial for open-angle glaucoma (OAG). PARTICIPANTS: The participants of this study were treatment-naive patients with newly diagnosed OAG, aged 46-78 years, with early to moderate glaucomatous visual field loss scheduled to be followed for 5 years within the study. METHODS: Patients were randomized to initial treatment with either topical monotherapy or with an intensive approach using drugs from three different classes, plus 360° laser trabeculoplasty. Changes in treatment were allowed. Standard automated perimetry and tonometry were performed and side-effects documented. All results are presented using intention-to-treat analysis. RESULTS: A total of 242 patients were randomized. After 3 years of follow-up, eight patients were lost to follow-up, six of whom were deceased. The median untreated baseline intraocular pressure (IOP) was 24 mmHg in both arms. The median IOP was almost constant over the 3 years of follow-up: ≈17 mmHg in the mono-arm and ≈14 mmHg in the multi-treatment arm. Treatment was intensified in 42% of the mono-treated patients and in 7% of the multi-treated patients. Treatment was reduced in 13% of the multi-treated patients. The median perimetric rate of progression was -0.5%/year in the mono-treated group and -0.1%/year in the multi-treated group (p = 0.03). CONCLUSION: The rate of disease progression was significantly slower in the multi-treated patients than in the mono-treated patients. Further follow-up will show whether this difference is sustained over time.

Screening for Open-Angle Glaucoma and Its Effect on Blindness.

PURPOSE: To evaluate the effect of population screening on low vision and blindness from open-angle glaucoma. DESIGN: Retrospective cohort study. METHODS: A large population-based screening for glaucoma was conducted in Malmö, Sweden, from 1992 to 1997. A total of 42,497 subjects were invited, of which 32,918 were screened, and 9,579 were non-responders (ie, did not participate). The records of glaucoma patients who had visited the Department of Ophthalmology at Malmö University Hospital from January 1, 1987, to December 31, 2017, were reviewed. Patients diagnosed at or after the screening were assessed for moderate or severe vision impairment, here called low vision, or blindness by the World Health Organization definition. Selection bias was corrected by creating a group of potential screening participants from a comparison group of clinical patients. Main outcome measures were the risk ratios of the cumulative incidence for bilateral low vision or blindness caused by glaucoma in screened patients compared with the potential participants. RESULTS: The cumulative incidence of blindness was 0.17% in the screened population versus 0.32% among the potential participants; and for low vision 0.25% versus 0.53%. The risk ratio (95% confidence interval) between the two was 0.52 (0.32-0.84) for blindness and 0.46 (0.31-0.68) for low vision. There were no differences between the proportions of potential confounders in the comparison group and those in the non-responders. CONCLUSIONS: The results suggest that population screening may reduce bilateral low vision and blindness caused by glaucoma by approximately 50%.

Laser trabeculoplasty in newly diagnosed multi-treated glaucoma patients.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of laser trabeculoplasty (LTP) in eyes which IOP had been substantially reduced by intensive topical treatment for one week. METHODS: Patients with newly diagnosed open-angle glaucoma were randomized to treatment with three IOP-lowering substances. One week later, 360° argon or selective LTP was performed. IOP was measured before LTP and at one-, three-, six- and 12-month post-LTP. The patients were part of the Glaucoma Intensive Treatment Study (GITS). RESULTS: Mean IOP (± SD) in 152 eyes of 122 patients was 14.0 (± 3.5) mmHg just before LTP. For every mmHg higher IOP prior to LTP, the IOP was reduced by an additional 0.6 mmHg at 12 months. The IOP was significantly reduced at all follow-up visits from -2.6 (± 3.1) mmHg at one month to -2.1 (± 3.8) mmHg at 12 months in eyes with pre-LTP IOP ≥ 15 mmHg, while no significant IOP reduction was seen in eyes with pre-LTP IOP < 15 mmHg. Older age, argon LTP and male sex were associated with larger IOP reduction after 12 months, whereas presence of exfoliation syndrome was associated with a smaller IOP reduction. No severe complications were reported. CONCLUSION: Success of LTP was highly dependent on the IOP level prior to LTP treatment. A sustained significant IOP reduction was seen in eyes with pre-LTP IOP ≥ 15 mmHg whereas no such effect was seen in eyes with pre-LTP IOP < 15 mmHg. Thus, LTP can be considered in eyes with multi-treatment when target pressure of < 15 mmHg is not achieved.

Initial intraocular pressure reduction by mono- versus multi-therapy in patients with open-angle glaucoma: results from the Glaucoma Intensive Treatment Study.

PURPOSE: To study newly diagnosed glaucoma patients given mono- or multi-therapy regarding differences in initial intraocular pressure (IOP) reduction, target IOP levels reached and influence of untreated baseline IOP on IOP reduction. METHODS: Patients newly diagnosed with manifest primary open-angle glaucoma and included in the Glaucoma Intensive Treatment Study (GITS) were randomized to immediate intensive treatment with any of three different IOP-lowering substances supplied in two bottles plus 360° laser trabeculoplasty or to conventional stepwise treatment starting with a single-drug. Intraocular pressure reduction was analysed 1 month after initiation of treatment. RESULTS: One hundred eighteen patients (143 eyes) received mono-therapy and 122 patients (152 eyes) multi-therapy. Median baseline IOP was 24.0 (min: 9.7, max: 56.0) mmHg in mono-therapy eyes and 24.0 (min: 12.3, max: 48.5) mmHg in multi-therapy eyes (p = 0.56). After 1 month in the two groups, respectively, values for median IOP reduction were 6.3 (range: -5.3-31.0) and 11.0 (range: 0.7-34.5) mmHg, and for mean relative decline 26.8 (range: -32.0-55.4) and 46.0 (range: 4.6-81.6) % (p = 0.000). A larger proportion of the multi-therapy patients reached each target IOP level (p = 0.000). The higher the baseline IOP, the larger the observed pressure reduction, considering both absolute and relative figures. The effect was more pronounced in eyes with multi-therapy than in those with mono-therapy (p = 0.000). For every mmHg higher IOP at baseline, the IOP was reduced by an additional 0.56 (mono-therapy) or 0.84 (multi-therapy) mmHg. CONCLUSION: Intensive treatment led to considerably greater IOP reduction than mono-therapy. Among patients with IOP ≥30 mmHg at diagnosis an IOP of <16 was reached in 2/3 of those with multi-therapy but in none with mono-therapy. The IOP reduction was highly dependent on the untreated IOP level.

The Glaucoma Intensive Treatment Study (GITS), a randomized clinical trial: design, methodology and baseline data.

PURPOSE: The primary objective of the ongoing Glaucoma Intensive Treatment Study (GITS) is to evaluate the effectiveness of immediate intensive treatment in comparison with the commonly recommended stepped regimen on the predicted visual field. The two treatment arms are also being compared regarding quality of life (QoL), intraocular pressure (IOP) reduction, frequency of reported side-effects, adverse events and adherence to prescribed treatment. DESIGN: A randomized, two-centre, prospective open-labelled treatment trial for open-angle glaucoma. PARTICIPANTS: Individuals aged 40-78 years with previously untreated and newly diagnosed glaucoma with early to moderate visual field loss were eligible. METHODS: Patients were randomized to initial treatment either using drug monotherapy in accordance with common glaucoma guidelines or using a more intensive approach including eyedrops containing drugs from three different classes combined with 360° laser trabeculoplasty. The patients are to be followed for 5 years at visits including standard automated perimetry, optical coherence tomography (OPT) and tonometry. Change of treatment is allowed and decided upon jointly with the patient as in conventional glaucoma management. MAIN OUTCOME: The estimated predicted preserved visual field and QoL at end of expected lifetime. RESULTS: A total of 242 patients, 45% females, mean age 68 years, were randomized. The median untreated IOP was 24 mm Hg, and the median visual field index (VFI), indicating the percentage of a full field, was 92%. CONCLUSION: Glaucoma Intensive Treatment Study is a clinical trial in which two groups of patients randomized to different initial intensities of IOP-reducing treatment are being compared with regard to rate of visual field progression and prediction of serious glaucomatous visual field loss at estimated at end of life.

Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for Glaucoma.

PURPOSE: The purpose of this study was to assess the intraocular pressure (IOP) - reducing effect of latanoprost in treatment-naïve patients with newly detected open-angle glaucoma with no restriction of the level of untreated IOP. METHODS: Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after initiation of treatment was recorded. RESULTS: Mean untreated IOP for all eyes was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9 mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in IOP ranged from -2.3 to 25.3 mm Hg after 1 month, and from -1.3 to 33.3 mm Hg after 3 months. The pressure-lowering effect was considerably more pronounced in eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg higher untreated IOP. Four eyes, with untreated IOP within statistically normal limits, had no or negative IOP-reduction. A regression model predicted that IOP reduction ended at untreated IOP≤16 mm Hg. Multiple regression analysis showed that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with pseudoexfoliation glaucoma. CONCLUSIONS: To the best of our knowledge, this paper is the first to report the IOP-reducing effect of latanoprost treatment at all untreated IOP levels in newly detected glaucoma patients. The effect was proportional to the untreated IOP at all levels above 16 mm Hg and better at higher untreated IOP levels, also in relative terms. Our results further confirm the indication of latanoprost as a first-line therapy for glaucoma.

The effect of different criteria on the number of patients blind from open-angle glaucoma.

BACKGROUND: The prevalence of blindness and visual impairment from glaucoma is influenced by the criteria used to define these entities, which differ between countries and regions, as well as among published reports. The objective of the present study was to ascertain the extent to which different criteria of blindness and visual impairment influence estimates of the number of patients classified as blind or visually impaired by glaucoma in a clinic-based population. METHODS: We conducted a retrospective chart review of 914 patients with open-angle glaucoma to compare numbers of patients identified as visually impaired with and without considering visual field status. We also compared proportions classified using World Health Organisation (WHO) and United States (US) blindness criteria, and applying a new US Social Security Administration (SSA) disability criterion: perimetric mean deviation (MD) ≤ -22 dB. RESULTS: Forty patients (4.4%) were bilaterally blind from glaucoma by the WHO criteria. Fifty-two (5.7%) were blind by the the US criterion. Assessing only visual acuity, 14 (1.5%) patients were blind by the WHO criteria and 24 (2.6%) by the US definition. Eighty-five (9.3%) met the US SSA disability criterion. Among those, 52 were impaired also by the WHO definition. No patients impaired according to the WHO criteria had MD values better than -22 dB. CONCLUSIONS: Excluding visual field status will seriously underestimate the prevalence of glaucoma blindness. In our patient population, 30% more patients were classified as blind by the US than by the WHO definition. Also, 60% more were identified as visually impaired by the US SSA criterion than by the WHO criteria. Visual field assessment is vital to determine visual impairment caused by glaucoma.