Differentiating Ischemic Optic Neuropathy from Glaucoma Using Diagnostic Tests.

INTRODUCTION: Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis. METHODS: The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date. RESULTS: Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes. CONCLUSION: By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.

Primary retinal tauopathy: A tauopathy with a distinct molecular pattern.

BACKGROUND: Phosphorylated tau (p-tau) accumulation, a hallmark of Alzheimer's disease (AD), can also be found in the retina. However, it is uncertain whether it is linked to AD or another tauopathy. METHODS: Retinas from 164 individuals, with and without AD, were analyzed for p-tau accumulation and its relationship with age, dementia, and vision impairment. RESULTS: Retinal p-tau pathology showed a consistent pattern with four stages and a molecular composition distinct from that of cerebral tauopathies. The stage of retinal p-tau pathology correlated with age (r = 0.176, P = 0.024) and was associated with AD (odds ratio [OR] 3.193; P = 0.001), and inflammation (OR = 2.605; P = 0.001). Vision impairment was associated with underlying eye diseases (ß = 0.292; P = 0.001) and the stage of retinal p-tau pathology (ß = 0.192; P = 0.030) in a linear regression model. CONCLUSIONS: The results show the presence of a primary retinal tauopathy that is distinct from cerebral tauopathies.

The effect of citicoline oral solution on quality of life in patients with glaucoma: the results of an international, multicenter, randomized, placebo-controlled cross-over trial.

PURPOSE: This study aims to evaluate whether the use of citicoline oral solution could improve quality of life in patients with chronic open-angle glaucoma (OAG). DESIGN: Randomized, double-masked, placebo-controlled, cross-over study was used. Patients were randomized to one of the two sequences: either citicoline 500 mg/day oral solution-placebo or placebo-citicoline 500 mg/day oral solution. Switch of treatments was done after 3 months; patients were then followed for other 6 months. Follow-up included 3-month, 6-month, and 9-month visits. OUTCOMES: The primary outcome was the mean change of "intra-patient" composite score of the Visual Function Questionnaire-25 (VFQ-25). after citicoline oral solution vs placebo at 6-month visit as compared with baseline. METHODS: The trial was multicenter, conducted at 5 European Eye Clinics. OAG patients with bilateral visual field damage, a mean deviation (MD) ranging from - 5 to - 13 dB in the better eye, and controlled IOP were included. VFQ-25 and SF-36 questionnaires were administered at baseline and at 3-, 6-, and 9-month visits. A mixed effect model, with a random effect on the intercept, accounted for correlations among serial measurements on each subject. RESULTS: The primary pre-specified outcome of the analysis reached statistical significance (p = 0.0413), showing greater improvement after citicoline oral solution. There was an increase in the composite score in both arms compared to baseline, but it was significant only for the placebo-citicoline arm (p = 0.0096, p = 0.0007, and p = 0.0006 for the three time-points compared to baseline). The effect of citicoline was stronger in patients with vision-related quality of life more affected by glaucoma at baseline. CONCLUSIONS: This is the first placebo-controlled clinical study evaluating the effect of a medical treatment aiming at improving vision-related quality of life in glaucomatous patients.

Lateralized Raise in Intraocular Pressure During Electroconvulsive Therapy: A Tonometry Pilot Study.

The aim of this study was to evaluate intraocular pressure (IOP) changes during and after electroconvulsive therapy. In 20 patients, IOP was measured using a handheld iCare tonometer before, during, and up to 15 minutes after the seizure. Electrode placement was either right unilateral (RUL) or bilateral (BL). Statistical analyses were done at baseline, during, and 15 minutes after the seizure. In the RUL group (n = 14), the IOP in the left eye increased from 14.8 mm Hg before the seizure to 27.8 mm Hg during the seizure ( P = 0.0001) and decreased to 14.0 mm Hg after the seizure ( P = 0.0002). The IOP in the right eye increased from 15.4 mm Hg before the seizure to 34.4 mm Hg during the seizure ( P = 0.0001) and decreased to 16.0 mm Hg after the seizure ( P = 0.0002). In the BL group (n = 6), the IOP in the left eye increased from 13.0 mm Hg before the seizure to 26.3 mm Hg during the seizure ( P = 0.1250) and decreased to 14.5 mm Hg after the seizure ( P = 0.250). In the right eye, the IOP increased from 13.3 mm Hg before the seizure to 28.4 mm Hg during the seizure ( P = 0.1250) and decreased to 13.7 mm Hg after the seizure ( P = 0.25). When the results were compared between the 2 electrode placements, the difference in IOP between the right and left eye was higher in the RUL group during (RUL 6.7 mm Hg vs BL 2.0 mm Hg, P = 0.0231) and after (RUL 2.1 mm Hg vs BL −0.8 mm Hg, P = 0.0492) the seizure. RUL stimulation with electroconvulsive therapy causes a rise in IOP that is partially lateralized, ipsilateral to the side of stimulation.

Treatment Outcomes Comparing the Paul and Baerveldt Glaucoma Implants After One Year of Follow-Up.

PRCIS: In reducing intraocular pressure (IOP), Paul (PGI) and Baerveldt (BGI) glaucoma implants are safe and effective in patients with glaucoma. OBJECTIVE: To compare efficacy and safety profiles of the PGI and BGI in the treatment of medically uncontrolled glaucoma at 1 year of follow-up. METHODS: Retrospective analysis of patients implanted with a PGI or BGI with a minimum of 12 months follow-up. The primary outcome was surgical success defined as IOP ≥6 and ≤18 mm Hg and at least 20% IOP reduction from baseline. Secondary outcomes included IOP measurements, number of medications, and complications. RESULTS: Twenty-three patients implanted with PGI and 27 with BGI were included. At last visit (12 mo), mean IOP had decreased from 23.7 ± 6.9 to 0.1 ± 2.9 mm Hg in the PGI group versus 26 ± 7.3 to 10.4 ± 4.9 mm Hg with the BGI ( P < 0.001 for both comparisons). Overall qualified success rates were similar between groups (PGI 91% vs BGI 89%, P = 0.784). IOP was significantly lower in the PGI at week 1 and month 1 of follow-up versus the BGI (13.6 ± 6.1 vs 20.1 ± 7.4; 14.6±3.8 vs 21.2 ± 5.8 mm Hg; P < 0.002 for both) with a lower number of medications (1.57 ± 1.47 vs 2.52 ± 1.16 at mo 1, P = 0.015). Most complications were minor and similar in both groups. CONCLUSION: Both PGI and BGI are safe and effective in reducing IOP in patients with glaucoma, with similar success rates.

Management of Childhood Glaucoma Following Cataract Surgery.

Glaucoma remains a frequent serious complication following cataract surgery in children. The optimal approach to management for 'glaucoma following cataract surgery' (GFCS), one of the paediatric glaucoma subtypes, is an ongoing debate. This review evaluates the various management options available and aims to propose a clinical management strategy for GFCS cases. A literature search was conducted in four large databases (Cochrane, PubMed, Embase, and Web of Science), from 1995 up to December 2021. Thirty-nine studies-presenting (1) eyes with GFCS; a disease entity as defined by the Childhood Glaucoma Research Network Classification, (2) data on treatment outcomes, and (3) follow-up data of at least 6 months-were included. Included papers report on GFCS treated with angle surgery, trabeculectomy, glaucoma drainage device implantation (GDD), and cyclodestructive procedures. Medical therapy is the first-line treatment in GFCS, possibly to bridge time to surgery. Multiple surgical procedures are often required to adequately control GFCS. Angle surgery (360 degree) may be considered before proceeding to GDD implantation, since this technique offers good results and is less invasive. Literature suggests that GDD implantation gives the best chance for long-term IOP control in childhood GFCS and some studies put this technique forward as a good choice for primary surgery. Cyclodestruction seems to be effective in some cases with uncontrolled IOP. Trabeculectomy should be avoided, especially in children under the age of one year and children that are left aphakic. The authors provide a flowchart to guide the management of individual GFCS cases.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

PURPOSE: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants. METHODS: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (Df ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist. RESULTS: Statistical models showed a significantly decreasing relationship between age and Df (linear: R-squared = 0.1897, p < 0.0001; quadratic: R-squared = 0.2343, p < 0.0001; cubic: R-squared = 0.2721, p < 0.0001), with the cubic regression model offering the best compromise between accuracy and model simplicity. Multivariate cubic regression showed that age, spherical equivalent and smoking behaviour have an effect (p < 0.0001) on Df . A significantly increasing effect of the number of pack-years on Df was observed (effect: 0.0004, p = 0.0017), as well as a significantly decreasing effect of years since tobacco abstinence (effect: -0.0149, p < 0.0001). CONCLUSION: We propose using a cubic trend with age, refractive error and smoking behaviour when interpreting retinal vessel complexity.

Patient creates filtering bleb: hypotony following traumatic rupture of an old scleral incision for intracapsular cataract surgery.

An 86-year-old woman presented with symptomatic hypotony on the left eye since a few weeks, blurry vision and a very sensitive eye. She had a history of bilateral intracapsular cataract extraction (ICCE) in 1982 and secondary intraocular lens implantation in 1988. The patient mentioned a fall on the left side of the head 6 months earlier. The diagnosis of a superior scleral fistula was made, confirmed by gonioscopy and anterior segment optical coherence tomography. Direct surgical repair of the fistula led to a favourable outcome. This case demonstrates the occurrence of symptomatic hypotony due to the traumatic creation of a scleral fistula with an inadvertent filtering bleb many years after ICCE, and the resolution of signs and symptoms after surgical repair. Conventional as well as contemporary modalities can be valuable in the assessment of such fistulae. Management depends on the clinical course and the mechanism and extent of fistulation.

Comparison of preserved bimatoprost 0.01% with preservative-free tafluprost: A randomised, investigator-masked, 3-month crossover, multicentre trial, SPORT II.

IMPORTANCE: This study compares the efficacy and tolerability of a preservative-free prostaglandin analogue (tafluprost 15 mg/ml) to a prostaglandin analogue that uses 0.02% of benzalkonium chloride (bimatoprost 0.1 mg/ml). BACKGROUND: Different prostaglandin analogues have been commercially approved, with differences in tolerability. DESIGN: Prospective, randomised, investigator-masked, 3-month crossover, multicentre trial. PARTICIPANTS: Sixty-four patients with ocular hypertension or open-angle glaucoma were randomised to two groups, after a 4-week washout period from their current topical drop regimen. METHODS: Participants were randomised to tafluprost (Group 1; n = 33) or bimatoprost (Group 2; n = 31). At month 3, each group switched to the opposite treatment. IOP was evaluated at multiple timepoints. MAIN OUTCOME MEASURES: The primary outcome was difference in mean IOP between the two groups at the final visit. Secondary outcomes included change from baseline IOP at month 3 and month 6, difference in mean IOP at month 3 and difference in IOP at all timepoints. Safety outcomes included best-corrected visual acuity (BCVA), adverse events, ocular tolerability, optic nerve assessment and slit lamp biomicroscopy. RESULTS: Both medications significantly lowered IOP at month 6 compared to baseline: 5.4 mmHg (27%) for tafluprost and 6.8 mmHg (33%) for bimatoprost (p < 0.0001). No significant differences in any of the safety measures (including conjunctival hypearemia) were detected. CONCLUSIONS AND RELEVANCE: Bimatoprost produced a statistically significant greater IOP reduction compared to tafluprost with minimal to no difference in side effects. This should be borne in mind when weighing up the pros and cons of preserved versus preservative-free prostaglandin analogue therapy. CLINICALTRIALS.GOV IDENTIFIER: NCT02471105.

The AppNL-G-F mouse retina is a site for preclinical Alzheimer's disease diagnosis and research.

In this study, we report the results of a comprehensive phenotyping of the retina of the AppNL-G-F mouse. We demonstrate that soluble Aß accumulation is present in the retina of these mice early in life and progresses to Aß plaque formation by midlife. This rising Aß burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in the AppNL-G-F mouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aß, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that the AppNL-G-F retina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.

Systematic Review on Fractal Dimension of the Retinal Vasculature in Neurodegeneration and Stroke: Assessment of a Potential Biomarker.

Introduction: Ocular manifestations in several neurological pathologies accentuate the strong relationship between the eye and the brain. Retinal alterations in particular can serve as surrogates for cerebral changes. Offering a "window to the brain," the transparent eye enables non-invasive imaging of these changes in retinal structure and vasculature. Fractal dimension (FD) reflects the overall complexity of the retinal vasculature. Changes in FD could reflect subtle changes in the cerebral vasculature that correspond to preclinical stages of neurodegenerative diseases. In this review, the potential of this retinal vessel metric to serve as a biomarker in neurodegeneration and stroke will be explored. Methods: A literature search was conducted, following the PRISMA Statement 2009 criteria, in four large bibliographic databases (Pubmed, Embase, Web Of Science and Cochrane Library) up to 12 October 2019. Articles have been included based upon their relevance. Wherever possible, level of evidence (LOE) has been assessed by means of the Oxford Centre for Evidence-based Medicine Level of Evidence classification. Results: Twenty-one studies were included for qualitative synthesis. We performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity precluded a meta-analysis. A significant association was found between decreased FD and neurodegenerative disease, mainly addressing cognitive impairment (CI) and dementia. In acute, subacute as well as chronic settings, decreased FD seems to be associated with stroke. Differences in FD between subtypes of ischemic stroke remain unclear. Conclusions: This review provides a summary of the scientific literature regarding the association between retinal FD and neurodegenerative disease and stroke. Central pathology is associated with a decreased FD, as a measure of microvascular network complexity. As retinal FD reflects the global integrity of the cerebral microvasculature, it is an attractive parameter to explore. Despite obvious concerns, mainly due to a lack of methodological standardization, retinal FD remains a promising non-invasive and low-cost diagnostic biomarker for neurodegenerative and cerebrovascular disease. Before FD can be implemented in clinic as a diagnostic biomarker, the research community should strive for uniformization and standardization.

The Prevalence of Undiagnosed Age-Related Sight-Threatening Diseases in Self-Proclaimed Healthy Individuals.

BACKGROUND: Age-related conditions such as glaucoma, age-related macular degeneration, diabetic retinopathy, and cataract have become the major cause of visual impairment and blindness in high-income countries. The aim of the current study is to investigate the prevalence of these eye diseases in a cohort of self-proclaimed healthy elderly and thus get a rough estimation of the prevalence of undiagnosed age-related eye conditions in the Belgian population. METHODS: Individuals aged 55 and older without ophthalmological complaints were asked to fill in a general medical questionnaire and underwent an ophthalmological examination, which included a biomicroscopic examination, intraocular pressure measurement, axial length measurement, and acquisition of fundus pictures and optical coherence tomography scans. Information regarding follow-up was collected in those who received the advice of referral to an ophthalmologist or the advice to have more frequent follow-up visits, based on their study evaluation. RESULTS: The cohort included 102 people and comprised 46% men (median age 70 years, range 57-85 years). Referral for additional examinations was made in 26 participants (25%). The advice to have more regular follow-up ophthalmologist visits was given to nine additional participants (9%). No significant correlations between baseline characteristics and the need for referral could be identified. Follow-up information was available for 25 out of 26 referred volunteers. Out of these, four underwent a therapeutic intervention based on study referral, up until 18 months after study participation. All four interventions took place in the age group 65-74 years. CONCLUSIONS: This study shows that, even in an elderly population with self-proclaimed healthy eyes and good general health, a significant proportion of subjects showed ocular findings that need regular follow-up and/or intervention. The frequency of prior ophthalmological examinations does not seem to be relevant to this proportion, meaning that everyone above 55 years old needs a routine ophthalmological evaluation.

Hyperspectral Imaging and the Retina: Worth the Wave?

Purpose: Hyperspectral imaging is gaining attention in the biomedical field because it generates additional spectral information to study physiological and clinical processes. Several technologies have been described; however an independent, systematic literature overview is lacking, especially in the field of ophthalmology. This investigation is the first to systematically overview scientific literature specifically regarding retinal hyperspectral imaging. Methods: A systematic literature review was conducted, in accordance with PRISMA Statement 2009 criteria, in four bibliographic databases: Medline, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Results: Fifty-six articles were found that meet the review criteria. A range of techniques was reported: Fourier analysis, liquid crystal tunable filters, tunable laser sources, dual-slit monochromators, dispersive prisms and gratings, computed tomography, fiber optics, and Fabry-Perrot cavity filter covered complementary metal oxide semiconductor. We present a narrative synthesis and summary tables of findings of the included articles, because methodologic heterogeneity and diverse research topics prevented a meta-analysis being conducted. Conclusions: Application in ophthalmology is still in its infancy. Most previous experiments have been performed in the field of retinal oximetry, providing valuable information in the diagnosis and monitoring of various ocular diseases. To date, none of these applications have graduated to clinical practice owing to the lack of sufficiently large validation studies. Translational Relevance: Given the promising results that smaller studies show for hyperspectral imaging (e.g., in Alzheimer's disease), advanced research in larger validation studies is warranted to determine its true clinical potential.

Accurate prediction of glaucoma from colour fundus images with a convolutional neural network that relies on active and transfer learning.

PURPOSE: To assess the use of deep learning (DL) for computer-assisted glaucoma identification, and the impact of training using images selected by an active learning strategy, which minimizes labelling cost. Additionally, this study focuses on the explainability of the glaucoma classifier. METHODS: This original investigation pooled 8433 retrospectively collected and anonymized colour optic disc-centred fundus images, in order to develop a deep learning-based classifier for glaucoma diagnosis. The labels of the various deep learning models were compared with the clinical assessment by glaucoma experts. Data were analysed between March and October 2018. Sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and amount of data used for discriminating between glaucomatous and non-glaucomatous fundus images, on both image and patient level. RESULTS: Trained using 2072 colour fundus images, representing 42% of the original training data, the trained DL model achieved an AUC of 0.995, sensitivity and specificity of, respectively, 98.0% (CI 95.5%-99.4%) and 91% (CI 84.0%-96.0%), for glaucoma versus non-glaucoma patient referral. CONCLUSIONS: These results demonstrate the benefits of deep learning for automated glaucoma detection based on optic disc-centred fundus images. The combined use of transfer and active learning in the medical community can optimize performance of DL models, while minimizing the labelling cost of domain-specific mavens. Glaucoma experts are able to make use of heat maps generated by the deep learning classifier to assess its decision, which seems to be related to inferior and superior neuroretinal rim (within ONH), and RNFL in superotemporal and inferotemporal zones (outside ONH).

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

Heterogeneity in arterial hypertension and ocular perfusion pressure definitions: Towards a consensus on blood pressure-related parameters for glaucoma studies.

PURPOSE: Glaucoma studies have long taken into account the blood pressure (BP) status of patients. This study summarizes and evaluates the impact of the different criteria that have been used for BP-related variables in glaucoma research. METHODS: Studies included in two meta-analyses that reviewed the role of BP in glaucoma were analyzed. Additional studies published after the search periods of the meta-analyses were also included. Criteria for the definition of arterial hypertension and other BP-related variables, such as mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP), were retrieved. RESULTS: Sixty-four studies were evaluated. One-third used 140 mmHg as a systolic BP cut-off to define hypertension, 20% used 160 mmHg and the remaining half used various other criteria. Less than 20% of studies reported MAP and/or MOPP. While eight of the ten studies reporting MAP used a correct formula that only happened for five of the eleven studies reporting MOPP. Using as an example average blood pressure values, incorrectly used formulas could have led to an overestimation of more than 100% of the expected values. CONCLUSION: Considerable heterogeneity exists in BP-related variables in glaucoma research and different definitions can lead to large disparities. Glaucoma research would benefit from a consensus regarding blood pressure parameters.

The vitreopapillary interface in healthy and glaucoma: posterior vitreous detachment in the vitreopapillary interface study.

PURPOSE: To investigate the vitreopapillary interface (VPI) in health and glaucoma according to the different stages of posterior vitreous detachment (PVD) formation. METHODS: Prospective single centre study including healthy subjects and glaucoma patients. PVD staging was performed with spectral domain optical coherence tomography. Gender, age, lens status and refractive error were assessed in both groups. Glaucoma patients additionally had a comprehensive ophthalmological investigation including intraocular pressure measurement, visual field testing and confocal imaging of the optic nerve head. RESULTS: Data on 523 subjects (993 eyes) were included from the VPI study (clinicaltrials.gov NCT02290795) database (493 eyes of 258 healthy subjects and 500 eyes of 265 glaucoma patients). Healthy subjects were significantly younger than primary open angle glaucoma patients (59.7 ± 14.81 versus 70.0 ± 10.78 years, p < 0.001), but were otherwise matched for refractive error and gender. Significantly more glaucomatous eyes were pseudophakic (26.6% versus 5.1%). Including only phakic nonoperated eyes from subjects between 50 and 80 years old decreased the age difference between healthy and open angle glaucoma (64.1 ± 8.0 versus 65.9 ± 6.7 years, p = 0.051). Comparing these subgroups rendered similar average ages for PVD stages 0 and 4, in contrast to the significant older age for the glaucoma subgroup in stage 1 (64.1 ± 6.01 versus 61.4 ± 8.38 years, p < 0.001) and a trend towards significance in stage 3 (70.8 ± 69.8 versus 67.5 ± 5.92 years, p = 0.051). CONCLUSION: The VPI study is a large clinical trial investigating the VPI in health and glaucoma. A subset of glaucoma patients seems to experience stages 1-3 of PVD formation at older age compared to healthy subjects.