Umeå University's logo

Aims: To estimate the changes in intraocular pressure (IOP) during the first 24 h after transscleral cyclophotocoagulation (TCP).

Methods: A prospective single-centre study, where patients with glaucoma destined for treatment with TCP were asked for participation. The IOP was measured prior to TCP and at 1, 2, 4, 6 and 24 h post-TCP. An IOP spike was defined as an elevation of IOP of ≥5 mmHg compared with baseline. The visual acuity (VA) was examined at baseline and after 24 h.

Results: The mean IOP prior to TCP in 58 eyes of 58 patients was 26.2 (±8.9 SD) mmHg. Twenty-three eyes (40%) experienced an IOP spike at some examination timepoint during the first 24 h. The mean value of the IOP spike was 12.1 (±6.9) mmHg. Fifty-six per cent of the eyes with pseudoexfoliation glaucoma (PEXG) experienced an IOP spike, and 16% had an IOP spike ≥20 mmHg. The IOP was significantly reduced at the 24 h examination by 8.1 (±7.8) mmHg (n = 58). The VA 24 h after TCP was unchanged compared with baseline.

Conclusion: Clinically significant IOP spikes were common in the first 24 h post-TCP. Almost one in five eyes had an increase of 10 mmHg and in almost one in 10 eyes, the IOP increase was 20 mmHg or higher. Eyes with PEXG had a higher occurrence of IOP spikes and displayed a greater magnitude of IOP elevation. Prophylactic post-operative IOP-lowering medication should be considered to prevent further glaucoma damage.

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 degrees 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.

PURPOSE: To assess the effect of an intensive initial intraocular pressure (IOP)–lowering treatment strategy on the progression of visual field damage. DESIGN: A randomized, controlled, open-label, 2-center clinical trial.

METHODS: A total of 242 patients with newly detected early or moderate untreated open-angle glaucoma were enrolled at 2 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 mm Hg in both treatment groups. During follow-up, median and mode IOP were 17 mm Hg in the mono- and 14 mm Hg in the multi-treatment group. In the mono-treatment group, the median VFI at projected end of life was 79.3% and in the multi-treatment group 87.1% (P =.15). The annual rate of progression of visual field damage was faster in mono-treatment than in multi-treatment participants; median losses per year were 0.65 and 0.25 percentage units, respectively (P =.09). Progression events occurred in 21% of the mono- and in 11% of the multi-treatment participants (P =.03). Adverse events, mostly mild, were reported in 25% of the mono- and in 36% of the multi-treatment 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.

CONCLUSIONS: In the overall analysis, the visual field outcomes were not overwhelmingly better in the multi-treatment group, but post hoc analysis showed definite benefit in patients with higher untreated IOP. Based on the results of this study, initial intensive treatment may be considered in glaucoma patients with high untreated IOP at diagnosis, although we found no evidence that multi-therapy should be given routinely to all glaucoma patients.

PURPOSE. To investigate whether nicotinamide (NAM) modulates retinal vasculature in glaucoma.

METHODS. This was a prospective controlled clinical trial investigating animal and human histopathology. Participants included normotensive and ocular hypertensive rats, postmortem human ocular tissue, glaucoma patients (n = 90), and healthy controls (n = 30). The study utilized histopathology, computer-assisted retinal vasculature analysis, optical coherence tomography angiography (OCTA), and NAM treatment. The main outcome measures included retinal vascular parameters in rats as assessed by AngioTool; retinal vasculature integrity in rats and humans as assessed by histopathology, antibody-staining, and ImageJ-based measurements; and retinal perfusion density (PD) and flux index in humans as assessed by OCTA.

RESULTS. A number of vessel parameters were altered in ocular hypertension/glaucoma compared to healthy controls. NAM treatment improved the retinal vasculature in ocular hypertensive rats, with an increase in mean vessel area, percentage area covered by vessels, total vessel length, total junctions, and junction density as assessed by AngioTool (all P < 0.05); vessel wall integrity as assessed by VE-cadherin antibody staining was also improved (P < 0.01). In humans, as assessed by OCTA, increases in PD in the optic nerve head and macula complete image (0.7%, P = 0.04 and 1.0%, P = 0.002, respectively) in healthy controls, and an increase in the temporal quadrant of the macula (0.7%, P = 0.02) in glaucoma patients was seen after NAM treatment.

CONCLUSIONS. NAM can prevent retinal vascular damage in an animal model of glaucoma. After NAM treatment, glaucoma patients and healthy controls demonstrated a small increase in retinal vessel parameters as assessed by OCTA.

Purpose: The purpose of this study was to examine the differences of optic nerve subarachnoid space (ONSAS) volume in patients with normal tension glaucoma (NTG) and healthy controls in different body positions.

Methods: Eight patients with NTG and seven healthy controls underwent magnetic resonance imaging (MRI) examinations in head up tilt (HUT) +11 degrees and head down tilt (HDT) -5 degrees positions according to a randomized protocol determining the starting position. The ONSAS volume in both body positions was measured and compared between the two groups. The results were analyzed using a generalized linear model.

Results: Between HDT and HUT, the postural ONSAS volume change was dependent on starting position (P < 0.001) and group (P = 0.003, NTG versus healthy). A subgroup analysis of those that were randomized to HUT examination first, coming directly from an upright position, showed that the patients with NTG had significantly larger positional ONSAS volume changes compared to the healthy controls; 121 ± 22 µL vs. 65 ± 37 µL (P = 0.049). Analysis of the ONSAS volume distribution showed different profiles for patients with NTG and healthy controls.

Conclusions: There was a significant difference in ONSAS volume change between patients with NTG and healthy subjects when subjected to posture changes, specifically when going from upright to head-down posture. This indicates that patients with NTG had been exposed to a lower ONSAS pressure when they came from the upright posture, which suggests an increased translaminar pressure difference in upright position. This may support the theory that NTG has a dysfunction in an occlusion mechanism of the optic nerve sheath that could cause abnormally negative ONSAS pressures in upright posture.

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.

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 degrees 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: approximate to 17 mmHg in the mono-arm and approximate to 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.

Purpose: To examine feasibility of phase-contrast magnetic resonance imaging (PCMRI) and to assess blood flow rate in the ophthalmic artery (OA) in patients with normal tension glaucoma (NTG) compared with healthy controls.

Methods: Sixteen patients with treated NTG and 16 age- and sex-matched healthy controls underwent PCMRI using a 3-Tesla scanner and ophthalmological examinations. OA blood flow rate was measured using a 2D PCMRI sequence with a spatial resolution of 0.35 mm(2).

Results: The blood flow rate in the NTG group was 9.6 +/- 3.9 ml/min [mean +/- SD] compared with 11.9 +/- 4.8 ml/min in the control group. Resistance Index (RI) and Pulsatility Index (PI) were 0.73 +/- 0.08 and 1.36 +/- 0.29, respectively, in the NTG group and 0.68 +/- 0.13 and 1.22 +/- 0.40, respectively, in the healthy group. The mean visual field index (VFI) was 46% +/- 25 for the worse NTG eyes. The measured differences observed between the NTG group and the control group in blood flow rate (p = 0.12), RI (p = 0.18) and PI (p = 0.27) were non-significant.

Conclusions: This case-control study, using PCMRI, showed a slight, but non-significant, reduction in OA blood flow rate in the NTG patients compared with the healthy controls. These results indicate that blood flow may be of importance in the pathogenesis of NTG. Considering that only a limited portion of the total OA blood flow supplies the ocular system and the large inter-individual differences, a larger study or more advanced PCMRI technique might give the answer.