Retinal Microvascular Dysfunction Occurs Early and Similarly in Mild Alzheimer's Disease and Primary-Open Angle Glaucoma Patients.

Purpose: To assess the similarities and differences in retinal microvascular function between mild Alzheimer's disease (AD) patients, early-stage primary open angle glaucoma (POAG) patients and healthy controls. Methods: Retinal vessel reactivity to flickering light was assessed in 10 AD, 19 POAG and 20 healthy age matched control patients by means of dynamic retinal vessel analysis (DVA, IMEDOS, GmbH, Jena, Germany) according to an established protocol. All patients additionally underwent BP measurements and blood analysis for glucose and lipid metabolism markers. Results: AD and POAG patients demonstrated comparable alterations in retinal artery reactivity, in the form of an increased arterial reaction time (RT) to flicker light on the final flicker cycle (p = 0.009), which was not replicated by healthy controls (p > 0.05). Furthermore, the sequential changes in RT on progressing from flicker one to flicker three were found to differ between healthy controls and the two disease groups (p = 0.001). Conclusion: AD and POAG patients demonstrate comparable signs of vascular dysfunction in their retinal arteries at the early stages of their disease process. This provides support for the concept of a common underlying vascular aetiology in these two neurodegenerative diseases.

Crossover Evaluation of Silicone Hydrogel Daily Disposable Contact Lenses.

PURPOSE: To assess the surface tear breakup time and clinical performance of three daily disposable silicone hydrogel contact lenses over 16 hours of wear. METHODS: Thirty-nine patients (mean [± SD] age, 22.1 [± 3.5] years) bilaterally wore (narafilcon A, filcon II-3, and delefilcon A) contact lenses in a prospective, randomized, masked, 1-week crossover clinical trial. Tear film was assessed by the tear meniscus height (TMH), ocular/contact lens surface temperature dynamics, and lens surface noninvasive breakup time at 8, 12, and 16 hours of wear. Clinical performance and ocular physiology were assessed by subjective questionnaire, by high-/low-contrast logMAR (logarithm of the minimum angle of resolution) acuity, and through bulbar and limbal hyperemia grading. Corneal and conjunctival staining were assessed after lens removal. RESULTS: Delefilcon A demonstrated a longer noninvasive breakup time (13.4 [± 4.4] seconds) than filcon II-3 (11.6 [± 3.7] seconds; p < 0.001) and narafilcon A (12.3 [± 3.7] seconds; p < 0.001). A greater TMH (0.35 [± 0.11] mm) was shown by delefilcon A than filcon II-3 (0.32 [± 0.10] seconds; p = 0.016). Delefilcon A showed less corneal staining after 16 hours of lens wear (0.7 [± 0.6] Efron grade) than filcon II-3 (1.1 [± 0.7]; p < 0.001) and narafilcon A (0.9 [± 0.7]; p = 0.031). Time was not a significant factor for prelens tear film stability (F = 0.594, p = 0.555) or TMH (F = 0.632, p = 0.534). Lens brand did not affect temperature (F = 1.220, p = 0.308), but it decreased toward the end of the day (F = 19.497, p < 0.001). Comfort, quality of vision, visual acuity and contrast acuity, and limbal grading were similar between the lens brands but decreased with time during the day (p < 0.05). CONCLUSIONS: The tear breakup time over the contact lens surface differed between lens types and may have a role in protecting the ocular surface.

The influence of end of day silicone hydrogel daily disposable contact lens fit on ocular comfort, physiology and lens wettability.

PURPOSE: To quantify the end-of-day silicone-hydrogel daily disposable contact lens fit and its influence of on ocular comfort, physiology and lens wettability. METHODS: Thirty-nine subjects (22.1±3.5 years) were randomised to wear each of 3 silicone-hydrogel daily-disposable contact lenses (narafilcon A, delefilcon A and filcon II 3), bilaterally, for one week. Lens fit was assessed objectively using a digital video slit-lamp at 8, 12 and 16h after lens insertion. Hyperaemia, non-invasive tear break-up time, tear meniscus height and comfort were also evaluated at these timepoints, while corneal and conjunctival staining were assessed on lens removal. RESULTS: Lens fit assessments were not different between brands (P>0.05), with the exception of the movement at blink where narafilcon A was more mobile. Overall, lag reduced but push-up speed increased from 8 to 12h (P<0.05), but remained stable from 12 to 16h (P>0.05). Movement-on-blink was unaffected by wear-time (F=0.403, P=0.670). A more mobile lens fit with one brand did not indicate that person would have a more mobile fit with another brand (r=-0.06 to 0.63). Lens fit was not correlated with comfort, ocular physiology or lens wettability (P>0.01). CONCLUSIONS: Among the lenses tested, objective lens fit changed between 8h and 12h of lens wear. The weak correlation in individual lens fit between brands indicates that fit is dependent on more than ocular shape. Consequently, substitution of a different lens brand with similar parameters will not necessarily provide comparable lens fit.

Systemic circulatory influences on retinal microvascular function in middle-age individuals with low to moderate cardiovascular risk.

PURPOSE: To investigate the relationship between retinal microvascular reactivity, circulatory markers for CVD risk and systemic antioxidative defence capacity in healthy middle-aged individuals with low to moderate risk of CVD. METHODS: Retinal vascular reactivity to flickering light was assessed in 102 healthy participants (46-60 years) by means of dynamic retinal vessel analysis (DVA). Other vascular assessments included carotid intima-media thickness (C-IMT) and blood pressure (BP) measurements. Total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and blood glutathione levels in its reduced (GSH) and oxidized (GSSG) forms were also determined for each participant, along with Framingham risk scores (FRS). RESULTS: Retinal arterial baseline diameter fluctuation (BDF) was independently, significantly and negatively influenced by LDL-C levels (ß = -0.53, p = 0.027). Moreover, the arterial dilation slope (SlopeAD ) was independently, significantly and positively associated with redox index (GSH: GSSG ratio, ß = 0.28, p = 0.016), while the arterial constriction slope (SlopeAC ) was significantly and negatively influenced by blood GSH levels (ß = -0.20, p = 0.042), and positively associated with FRS (ß = 0.25, p = 0.009). Venous BDF and dilation amplitude (DA) were also negatively influenced by plasma LDL-C levels (ß = -0.83, p = 0.013; and ß = -0.22, p = 0.028, respectively). CONCLUSIONS: In otherwise healthy individuals with low to moderate cardiovascular risk, retinal microvascular dilation and constriction responses to stress levels are influenced by systemic antioxidant capacity, and circulating markers for cardiovascular risk.

Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels.

BACKGROUND: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. METHODS: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). RESULTS: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). CONCLUSIONS: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity.

Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma.

PURPOSE: To investigate in parallel the systemic glutathione levels of patients suffering from primary open angle glaucoma (POAG) or normal tension glaucoma (NTG) with comparable functional loss. METHODS: Thirty-four POAG patients, 30 NTG patients, and 53 controls were subjected to blood analysis to detect the level of circulating glutathione in its reduced (GSH) and oxidized (GSSG) forms. Systemic blood pressure (BP) and ocular perfusion pressure (OPP) parameters were also determined. RESULTS: Independent of age, POAG and NTG patients demonstrated significantly lower GSH and t-GSH levels than age-matched controls (P < 0.001). Additionally, a lower redox index was found, but in POAG patients only, in comparison to both NTG and control groups (P = 0.020). GSSG levels were, however, similar between all study groups (P > 0.05). CONCLUSIONS: This study demonstrates, for the first time, that both POAG and NTG patients exhibit lower GSH and t-GSH levels than age-matched controls, indicating a similar general compromise of the antioxidant defense systems may exist in both conditions.

Primary open-angle glaucoma vs normal-tension glaucoma: the vascular perspective.

OBJECTIVE: To compare and contrast the presence of ocular and systemic vascular function in patients with newly diagnosed and previously untreated primary open-angle glaucoma (POAG) vs those with normal-tension glaucoma (NTG) and comparable early-stage, functional loss. METHODS: The systemic vascular function of 19 patients with POAG, 19 patients with NTG, and 20 healthy individuals serving as controls was assessed using 24-hour ambulatory blood pressure monitoring, peripheral pulse-wave analysis, and carotid intima-media thickness. Retinal vascular reactivity to flicker light was assessed using dynamic retinal vessel analysis (Imedos, GmbH). RESULTS: Compared with controls, patients with POAG and those with NTG exhibited similarly increased nocturnal systemic blood pressure variability (P = .01), peripheral arterial stiffness (P = .02), carotid intima-media thickness (P = .04), and reduced ocular perfusion pressure (P < .001). Furthermore, on dynamic retinal vessel analysis, both glaucoma groups exhibited steeper retinal arterial constriction slopes after cessation of flicker (P = .007) and a similarly increased fluctuation in arterial and venous baseline diameter (P = .008 and P = .009, respectively) compared with controls. CONCLUSIONS: Patients with POAG or NTG exhibit similar alterations in ocular and systemic circulation in the early stages of their disease process. This finding highlights the importance of considering vascular risk factors in both conditions and raises questions about the current separation of the two conditions into distinct clinical entities.

Coexistence of macro- and micro-vascular abnormalities in newly diagnosed normal tension glaucoma patients.

PURPOSE: To investigate the coexistence of ocular microvascular and systemic macrovascular abnormalities in early stage, newly diagnosed and previously untreated normal tension glaucoma patients (NTG). METHODS: Retinal vascular reactivity to flickering light was assessed in 19 NTG and 28 age-matched controls by means of dynamic retinal vessel analysis (IMEDOS GmbH, Jena, Germany). Using a newly developed computational model, the entire dynamic vascular response profile to flicker light was imaged and used for analysis. In addition, assessments of carotid intima-media thickness (IMT) and pulse wave analysis (PWA) were conducted on all participants, along with blood pressure (BP) measurements and blood analyses for lipid metabolism markers. RESULTS: Patients with NTG demonstrated an increased right and left carotid IMT (p = 0.015, p = 0.045) and an elevated PWA augmentation index (p = 0.017) in comparison with healthy controls, along with an enhanced retinal arterial constriction response (p = 0.028), a steeper retinal arterial constriction slope (p = 0.031) and a reduced retinal venous dilation response (p = 0.026) following flicker light stimulation. CONCLUSIONS: Early stage, newly diagnosed, NTG patients showed signs of subclinical vascular abnormalities at both macro- and micro-vascular levels, highlighting the need to consider multi-level circulation-related pathologies in the development and progression of this type of glaucoma.