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Purpose: Glaucoma is characterized by progressive retinal ganglion cell degeneration. Nicotinamide supplementation has demonstrated neuroprotective potential in glaucoma by raising retinal and optic nerve nicotinamide adenine dinucleotide (NAD) via the salvage pathway, dependent on nicotinamide phosphoribosyltransferase (NAMPT). The NAMPT is essential for retinal function, and its extracellular form (eNAMPT) has been detected in blood. Reduced circulating eNAMPT could indicate impaired NAD biosynthetic capacity and glaucomatous neurodegeneration susceptibility.

Methods: We (i) developed a specific, semiquantitative assay to detect plasma eNAMPT, (ii) explored its potential as biomarker, and (iii) assessed the effect of 2-week nicotinamide supplementation on circulating levels. This was done in samples from a prospective clinical trial at the Eye Clinic, Umeå University Hospital (Sweden), including 30 controls and 90 patients with glaucoma.

Results: A Western blotting assay was designed, detecting eNAMPT (52 kilodalton [kDa]) and transferrin (77 kDa) as housekeeping protein from 0.2 µL EDTA-plasma. Intra- and inter-assay variability were 14.9% and 37.9%, respectively. eNAMPT levels showed no difference between glaucoma and controls, nor changes after supplementation.

Conclusions: eNAMPT is readily and specifically detected by Western blotting in plasma from healthy controls and patients with glaucoma. Given the role of NAD/NAMPT in neurodegeneration, this study provides a platform for specific detection of eNAMPT in liquid biopsies. Further studies specifically designed to study eNAMPT are needed to clarify its role in retinal ganglion cell degeneration and the therapeutic response to nicotinamide.

Translational Relevance: This study established a method to sensitively detect plasma eNAMPT of patients with glaucoma and controls, providing a basis for future biomarker development.

Aim: To evaluate the impact of initial mono- versus multitherapy on the ocular surface and related quality of life after 5 years follow-up in the Glaucoma Intensive Treatment Study (GITS).

Method: The study included patients with primary open-angle glaucoma and pseudoexfoliation glaucoma who completed 5-year follow-up in GITS. Assessment of ocular surface disease (OSD) symptoms was done using a Swedish Translation of the OSD Index (OSDI). Signs of OSD were assessed with tear break-up time (BUT), Schirmer I test and staining using Lissamine green. Rasch analysis was used to analyse OSDI results.

Results: Data on OSD symptoms were available at 5 years in 90% (219/242) of all participants initially included in GITS. Subjective or objective OSD findings did not differ significantly between mono- and multitherapy. More than 90% of patients in both arms reported no or little subjective ocular surface problems and showed no or minimal staining with Lissamine green at the 60-month visit. Furthermore, 46% had normal BUT and 60% normal Schirmer tests. Use of preservative-free drops or need for additive lubricating tear drops did not differ between the arms.

Conclusion: We found no differences in objective or subjective impact on ocular surface between the two randomization arms. However, a subgroup of glaucoma patients had more severe OSD irrespective of the amount of topical glaucoma treatment received, and this should be considered when choosing glaucoma therapy treatment in this subgroup by considering laser treatment or non-preserved eye drops.

We designed and synthesized a series of novel 1,2,3,4-tetrahydroquinoxaline derivatives and evaluated their ability to increase nicotinamide adenine dinucleotide (NAD) levels in primary cortical neurons. Several compounds demonstrated nanomolar potency and enabled the establishment of clear structure–activity relationships (SAR), highlighting key substituents required for activity. Qualitative 3DSAR analysis further identified favorable steric, electrostatic, and hydrophobic features associated with NAD enhancement. Selected lead compounds were assessed for in vitro drug metabolism and pharmacokinetics (DMPK) properties, showing good cell permeability and species-dependent metabolic stability in liver microsomes, with improved stability in human systems compared with rodent systems. These findings identify tetrahydroquinoxalines as a promising class of neuronal NAD-boosting agents and provide a strong foundation for further optimization toward neuroprotective drug candidates.

Purpose: To investigate the characteristics of referral for glaucoma surgery and compare surgical practices in various European regions in 2025.

Methods: Data of 300 eyes of 300 consecutive patients undergoing glaucoma surgery were analysed using a standardized questionnaire and compared between geographical regions. Glaucoma specialists from one centre per country provided data on demographics, glaucoma types, intraocular pressure (IOP), visual field and structural metrics, types of surgery and referral timeliness (timely, later than optimal, late).

Results: The median (quartiles) age was 72 (64–78) years. Primary open angle glaucoma (52.0%) and pseudoexfoliative glaucoma (23.0%) were the most common glaucoma types. Median disease duration was 75 (28–144) months, preoperative IOP 22 (18–28) mmHg, mean deviation − 14.47 (− 21.60 to − 7.85) dB, and retinal nerve fibre layer thickness 60 (50–75) µm. Trabeculectomy (38.3%), minimally invasive bleb forming surgeries (28.3%), and drainage devices (11.3%) were the predominant procedures; 18.7% of the surgeries were combined with phacoemulsification. More severe disease was associated with filtering or drainage device surgery (p < 0.001). Referral was timely in 34.7%, later than optimal in 35.7%, and late in 29.7%. Late referrals were associated with higher IOP, more advanced MD, and thinner RNFL (p < 0.001). Regional differences were significant for common glaucoma types (p = 0.013) and surgical choice (p < 0.0001). Late and later-than-optimal referrals ranged between 22% and 38.3%, and 30.0% and 41.7% between the regions, respectively. The proportion of timely referrals in the East European region (20%) was significantly lower than that in the South and West European (approximately 40%) and North European (31.7%) regions (p = 0.019).

Conclusions: Marked differences exist in Europe in glaucoma referral timeliness and surgical practice. Late referral remains frequent and associated with advanced structural and functional damage in Europe.

In glaucoma, retinal ganglion cell degeneration has been linked to declining mitochondrial metabolic capacity. Nicotinamide (NAM) supplementation has emerged as a potential treatment for this. We assessed the effects of a 2-week NAM supplementation on blood buffy coat mitochondrial content (qPCR to assess mtDNA amount per cell) and the plasma metabolome (small-molecular-weight high-resolution mass spectrometry) in 90 glaucoma subjects from 3 different glaucoma subtypes (high tension glaucoma (HTG), normal tension glaucoma (NTG), and pseudoexfoliative glaucoma (PEXG), n = 30 per group), and 30 healthy controls with similar age and sex distribution. At baseline (pre-NAM), only ethylmalonic acid, a compound related to defects in β-oxidation and mitochondrial dysfunction, was found to be modestly increased in the 3 glaucoma subtypes in comparison to controls. All groups showed a similar metabolome response to treatment with a specific increase in NAM and related species (1-methylnicotinamide, 6-hydroxynicotinamide, N1-methyl-2-pyridone-5-carboxamide), increased 5-methylcytosine, and decreased 4-pyridoxic acid. Between groups, only sarcosine had a different response, with a small reduction in HTG and NTG post-treatment. NAM treatment resulted in a significant but slight within-group increase in blood mtDNA amount in controls and HTG (12 % and 17 %, respectively). This study suggests that NAM treatment leads to similar plasma metabolome changes between glaucoma groups and controls, which predominantly reflect increased NAM metabolites and intermediates, with minimal effects on the wider metabolome, and a modest increase in mtDNA amount in HTG and controls. As this was observed in a short-term accelerated dosing context, long-term and larger studies with additional timepoints and greater adjustment for systemic metabolic factors will be required to provide more information on the long-term effects of oral NAM supplementation.

Glaucoma is a progressive, age-related eye disease. One in six patients progresses to bilateral blindness. There is no curative treatment, but lowering the intraocular pressure can stabilize the disease. Regular monitoring for disease progression is recommended to enable timely evaluation and intervention. To investigate the adherence of eye clinics to the planned control intervals, a nationwide survey was conducted May 6-10, 2019. Of the 167 identified outpatient eye clinics, 120 answered the questionnaire with a total of 6,122 patient visits recorded. More patients were examined with measurements of visual field and imaging of the optic nerve head, compared with a previous survey in 2005. Extension of the planned intervals between visits was often considerable and varied dramatically between clinics, counties, and regions. The waiting times were generally shorter at private clinics. In conclusion, the results show that glaucoma care is not equal in Sweden and can, therefore, create risks for irreversible visual damage to patients. 

Purpose: The purpose of this study was to create a prototype master protocol for benchmarking glaucoma real-world data (RWD). Benchmarking is part of the digital innovation strategy of the Finnish aces-rwm ecosystem (automation of care and evaluation of the system with real-world monitoring).

Methods: We collected glaucoma RWD in 2012–17 at Tampere University Hospital (Tays) and compared them to six published RWD sets (one in Sweden and five in England). Visual field (VF) data at Tays were retrieved from the perimeter, and clinical RWD were collected manually. At baseline, VF data were available in 2511 of 4121 glaucoma patients (61%), of whom 1413 patients (56%) had 5 years of VF follow-up by 2017 (34% of all 4121 patients). Mean deviation (MD) data were analysed in multiple ways, considering also age and intraocular pressure (IOP).

Results: In most data sets, higher age was related to faster progression. At Tays, the distributions of progression rates were similar in better and worse eyes. The proportions of eyes at Tays with the medium rate of MD progression (17% for 0.5–1.5 dB/year) and the fast rate (6% for >1.5 dB/year) were similar to the published RWD trial in England. The published datasets show significant variability in how their findings were reported.

Conclusions: This study represents a first step toward the development of a master protocol for real-world benchmarking of glaucoma care. Further refinement of the protocol will encourage and require national and international collaboration in order to produce comprehensive and comparable real-world EHR data sets.

Purpose: To compare the 12-month outcomes of cataract surgery combined with iStent Inject W or Kahook Dual Blade Glide versus cataract surgery alone.

Design: A prospective, randomized controlled trial conducted at a single center in Sweden.

Participants: Adult patients with cataract and medically treated ocular hypertension or mild to advanced primary open-angle glaucoma or pseudoexfoliative glaucoma.

Methods: Patients were randomized 1:1:1 to cataract surgery with iStent Inject W (cataract-iStent group, n = 40), cataract surgery with Kahook Dual Blade Glide (cataract-KDB group, n = 40), or cataract surgery alone (cataract group, n = 40), and followed for 12 months.

Main Outcome Measures: The primary effectiveness endpoints were surgical success, defined as a reduction in intraocular pressure (IOP) of ≥20% or a reduction of ≥1 medication, and change in IOP and ocular hypotensive medications at 12 months. Secondary endpoints included threshold IOP levels and adverse events.

Results: At 12 months, the rate of surgical success was higher in the cataract-iStent and cataract-KDB groups compared to the cataract group (87.5% vs. 52.5%, P < 0.001). Mean reduction in IOP was similar between groups (–3.0, –3.5, and –2.8 mmHg, P = 0.755), while reduction in medication was higher in the cataract-iStent and cataract-KDB groups compared to the cataract group (–0.8 and –0.9 vs. –0.4, P = 0.01). The main adverse events were transient hyphema (15% in the cataract-KDB group) and IOP spikes (37.5% in the cataract group, 10% in the cataract-iStent group, and 15% in the cataract-KDB group, P = 0.006). Additional glaucoma surgery was required in 1 eye (in the cataract group), and added therapy or selective laser trabeculoplasty was required in 4 eyes (3 in the cataract group and 1 in the cataract-KDB group).

Conclusions: Combined cataract surgery with iStent Inject W or Kahook Dual Blade Glide achieved significantly greater surgical success compared to cataract surgery alone, and this was due to a greater reduction in number of hypotensive medications.

Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The EGS Guidelines are an evidence-based handbook for the care and management of glaucoma patients across Europe and worldwide.

Developed by the European Glaucoma Society (EGS), they are created for the entire scientific and medical community, providing a comprehensive and up-to-date reference for all specialists involved in glaucoma care.