Correction to: Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial.

The article "Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial", written by Martin Kallab, Stephan Szegedi, Nikolaus Hommer, Hannes Stegmann, Semira Kaya, René M. Werkmeister, Doreen Schmidl, Leopold Schmetterer, Gerhard Garhöfer was originally published electronically on the publisher's internet portal (currently SpringerLink) on November 19, 2019 without open access.

Topical Low Dose Preservative-Free Hydrocortisone Reduces Signs and Symptoms in Patients with Chronic Dry Eye: A Randomized Clinical Trial.

PURPOSE: Dry eye disease (DED) is a highly prevalent ocular condition with a significant burden on affected patients. Regardless of the underlying etiology, DED is associated with increased ocular surface inflammation. We investigated the safety and efficacy of a short-term treatment with topical low dose hydrocortisone in patients with chronic DED and ocular surface inflammation. METHODS: A total of 60 patients (mean age 51 ± 14 years) with chronic DED and conjunctival hyperemia greater than grade 2 on the Efron scale were included. Patients were randomized to receive either preservative-free hydrocortisone 0.335% (Softacort, Laboratories Thea, France) for 12 days four times daily followed by 2 days twice daily instillation (intense treatment group) or 8 days three times daily followed by 3 days twice daily treatment (standard treatment group). Ocular redness was assessed at baseline, day 14, and day 28. Measurement of intraocular pressure (IOP) and clinical tests to assess signs and symptoms of DED were performed. RESULTS: Conjunctival hyperemia and Ocular Surface Disease Index (OSDI) significantly decreased in both treatment groups (p < 0.001 each) after hydrocortisone treatment. A significant increase in tear film thickness was seen 4 weeks after treatment start (p = 0.03 and p = 0.04, respectively). IOP did not change in either of the two treatment groups (p = 0.45). CONCLUSION: Treatment with low dose hydrocortisone 0.335% reduced ocular inflammation and decreased OSDI score. No change in IOP was observed in either of the two treatment schedules. Because of its good safety profile, low dose hydrocortisone may be an interesting alternative to standard corticosteroid treatment in DED. FUNDING: Laboratories Thea. TRIAL REGISTRATION: Clinicaltrials.gov registry: NCT03907865.

A Controlled, Randomized Double-Blind Study to Evaluate the Safety and Efficacy of Chitosan-N-Acetylcysteine for the Treatment of Dry Eye Syndrome.

PURPOSE: This study was designed to evaluate the effect of chitosan-N-acetylcysteine (C-NAC) eye drops on tear film thickness (TFT) in patients with dry eye syndrome (DES). METHODS: This was a controlled, randomized, double-blind clinical investigation with patients assigned to 2 cohorts. In Cohort I, 21 patients were randomized to receive 1 instillation of C-NAC eye drops in 1 eye and placebo (normal saline solution) in the contralateral eye. In Cohort II, 17 patients were randomized to receive C-NAC eye drops once (QD) or twice (BID) daily for 5 days. TFT was assessed with a custom-built ultrahigh-resolution optical coherence tomography system. RESULTS: In Cohort I, mean TFT increased from 3.9 ± 0.5 µm predose to 4.8 ± 1.1 µm 10 min postdose after treatment with C-NAC. The increase was significantly different from placebo over time (P < 0.0001) and remained stable until 24 h postdose. In Cohort II, TFT increased with QD and BID instillation, with no significant difference between regimens. In both groups, Ocular Surface Disease Index scores improved, fewer patients presented with corneal damage, and symptoms of ocular discomfort/conjunctival redness were reduced. CONCLUSIONS: A single instillation of C-NAC significantly increased mean TFT in patients with DES as early as 10 min after instillation and lasted for 24 h. The magnitude of the increase in TFT following a single instillation was comparable with that after instillation twice daily over 5 days. Corneal damage improved in >60% of patients. C-NAC could be a viable treatment option for DES.

Tear film thickness after treatment with artificial tears in patients with moderate dry eye disease.

PURPOSE: This study was designed to investigate the effect of a single-drop instillation of different lacrimal substitutes on tear film thickness (TFT) assessed with optical coherence tomography in patients with mild to moderate dry eye disease. METHODS: The study was performed in a randomized, double-masked, controlled parallel group design. Patients received a single dose of either unpreserved trehalose 30 mg/mL and sodium hyaluronate 1.5 mg/mL (TH-SH, Thealoz Duo), unpreserved sodium hyaluronate, 0.15% (HA, Hyabak) or sodium chloride, 0.9% (NaCl, Hydrabak) eye drops. Sixty patients finished the study according to the protocol. TFT was measured with a custom-built ultrahigh-resolution Fourier domain optical coherence tomography system providing a resolution of 1.2 µm. RESULTS: The mean TFT before treatment was 2.5 ± 0.4 µm. Ten minutes after instillation, TFT significantly increased in the TH-SH group from 2.4 ± 0.4 to 3.1 ± 0.9 µm (P < 0.01) and in the HA group from 2.4 ± 0.3 to 2.9 ± 0.5 µm (P < 0.01), whereas no significant change was observed in the NaCl group (from 2.6 ± 0.4 to 2.7 ± 0.4 µm, P = 0.76). The increase in TFT remained statistically significant up to 240 minutes after administration of TH-SH. In contrast, the increase in TFT after administration of HA was only statistically significant at 10, 20, and 40 minutes after drop instillation. CONCLUSIONS: The findings of this study indicate that single instillation of TH-SH and HA eye drops increases TFT in patients with dry eye disease. The data also indicate longer corneal residence of the TH-containing eye drops. The effect of multiple instillation and long-term use of artificial tears on TFT warrants further investigation.

The association between subjective and objective parameters for the assessment of dry-eye syndrome.

PURPOSE: The aim of the present study was to evaluate the association between symptoms and different clinical signs in patients with dry-eye syndrome (DES). METHODS: Fifty-two patients with DES were included in the present cross-sectional study. For assessment of symptoms, the Ocular Surface Disease Index (OSDI) was used. Clinical parameters included measurement of tear break up time (BUT), corneal fluorescein staining, tear osmolarity, and ocular scattering index (OSI). Tear film thickness (TFT) was assessed using a custom-built optical coherence tomography (OCT) system with an axial resolution of 1.2 µm. In addition, impression cytology was performed. Correlation coefficients were calculated using linear regression analysis. RESULTS: The mean OSDI in the present study population was 28.9 ± 17.6, the mean TFT was 4.1 ± 1.3 µm. A significant negative correlation was found between OSDI and TFT (r = -0.34, P = 0.01). Tear film thickness correlated positively with BUT (r = 0.35, P = 0.01), but with no other signs of DES. No association was found between OSDI and the other evaluated signs. CONCLUSIONS: The study population mainly comprised of patients with mild to moderate DES. Tear film thickness as measured with a custom-built OCT device correlated with subjective symptoms in these patients. In agreement with previous data, the association between other signs and symptoms was weak in the present study. Measurement of TFT with OCT may become a valuable tool in the management of DES patients. (ClinicalTrials.gov number, NCT01753687.)

Effect of hyaluronic acid on tear film thickness as assessed with ultra-high resolution optical coherence tomography.

PURPOSE: The aim of this study was to assess the effect of a single drop of hyaluronic acid on tear film thickness (TFT) in healthy subjects. METHODS: Sixteen healthy subjects (eight male/eight female) aged between 20 and 36 years were included in this randomized, double-masked placebo-controlled study. One eye received a single dose of hyaluronic acid (Olixia pure(®) ; Croma Pharma, Korneuburg, Austria) eye drops, and the fellow eye received physiologic saline solution as placebo control. The study eye was chosen randomly. TFT as measured with a custom-built Fourier-domain optical coherence tomography (FD-OCT) system was the main outcome variable and measured before and every 10 min until 1 hr after topical administration. RESULTS: Baseline TFT was 4.8 ± 0.5 µm in the study eye and 5.0 ± 0.4 µm in the control eyes. Hyaluronic acid significantly increased TFT (p = 0.008 versus placebo) with a maximum effect 10 min after instillation (13.9 ± 11.9%). Post hoc analysis revealed that an increase in TFT was seen until 30 min after administration compared to placebo. Data in the placebo group show high reproducibility with an intraclass correlation coefficient of 0.93 and a coefficient of variation of 5.4 ± 3.3%. CONCLUSION: The data of this study indicate that hyaluronic acid increases TFT for as long as 30 min in healthy subjects. In addition, our data provide evidence that our custom-built OCT system is capable of measuring residence time of lubricants on the ocular surface.

Regulation of retinal oxygen metabolism in humans during graded hypoxia.

Animal experiments indicate that the inner retina keeps its oxygen extraction constant despite systemic hypoxia. For the human retina no such data exist. In the present study we hypothesized that systemic hypoxia does not alter inner retinal oxygen extraction. To test this hypothesis we included 30 healthy male and female subjects aged between 18 and 35 years. All subjects were studied at baseline and during breathing 12% O2 in 88% N2 as well as breathing 15% O2 in 85% N2. Oxygen saturation in a retinal artery (SO2art) and an adjacent retinal vein (SO2vein) were measured using spectroscopic fundus reflectometry. Measurements of retinal venous blood velocity using bidirectional laser Doppler velocimetry and retinal venous diameters using a Retinal Vessel Analyzer (RVA) were combined to calculate retinal blood flow. Oxygen and carbon dioxide partial pressure were measured from earlobe arterialized capillary blood. Retinal blood flow was increased by 43.0 ± 23.2% (P < 0.001) and 30.0 ± 20.9% (P < 0.001) during 12% and 15% O2 breathing, respectively. SO2art as well as SO2vein decreased during both 12% O2 breathing (SO2art: -11.2 ± 4.3%, P < 0.001; SO2vein: -3.9 ± 8.5%, P = 0.012) and 15% O2 breathing (SO2art: -7.9 ± 3.6%, P < 0.001; SO2vein: -4.0 ± 7.0%, P = 0.010). The arteriovenous oxygen difference decreased during both breathing periods (12% O2: -28.9 ± 18.7%; 15% O2: -19.1 ± 16.7%, P < 0.001 each). Calculated oxygen extraction did, however, not change during our experiments (12% O2: -2.8 ± 18.9%, P = 0.65; 15% O2: 2.4 ± 15.8%, P = 0.26). Our results indicate that in healthy humans, oxygen extraction of the inner retina remains constant during systemic hypoxia.

Role of nitric oxide in optic nerve head blood flow regulation during an experimental increase in intraocular pressure in healthy humans.

The present study set out to investigate whether nitric oxide, a potent vasodilator, is involved in the regulatory processes in optic nerve head blood flow during an experimental increase in intraocular pressure (IOP). The study was conducted in a randomized, double-masked, placebo-controlled, three way cross-over design. 12 healthy subjects were scheduled to receive either L-NMMA (an unspecific nitric oxide synthase inhibitor), phenylephrine (an α-adrenoceptor agonist) or placebo on three different study days. Optic nerve head blood flow was measured using laser Doppler flowmetry and IOP was increased stepwise with a suction cup. Mean arterial pressure (MAP) and IOP were measured non-invasively and ocular perfusion pressure (OPP) was calculated as OPP = 2/3 MAP-IOP. Administration of L-NMMA and phenylephrine significantly increased MAP and therefore OPP at rest (p < 0.01). L-NMMA significantly reduced baseline blood flow in the optic nerve head (p < 0.01). Application of the suction cup induced a significant increase in IOP and a decrease in OPP (p < 0.01). During the stepwise increase in IOP, some autoregulatory potential was observed until OPP decreased approximately -30% below baseline. None of the administered substances had an effect on this autoregulatory behavior (p = 0.49). The results of the present study confirm that the human optic nerve head shows some regulatory capacity during a decrease in OPP. Nitric oxide is involved in the regulation of basal vascular tone in the optic nerve head but does not seem to be involved in the regulatory mechanisms during an acute increase in IOP in young healthy subjects.

Regulation of optic nerve head blood flow during combined changes in intraocular pressure and arterial blood pressure.

In the choroid, there is evidence that blood flow does not only depend on ocular perfusion pressure (OPP), but also on absolute mean arterial pressure (MAP) and intraocular pressure (IOP). The present study included 40 healthy subjects to investigate whether such behavior is also found in the optic nerve head (ONH). The ONH blood flow (ONHBF) was studied using laser Doppler flowmetry during a separate increase in IOP and MAP as well as during a combined elevation. Mean arterial pressure was increased by isometric exercise and IOP by the suction method. During both, the change in ONHBF was less pronounced than the change in OPP indicating autoregulation. Correlation analysis was performed for the combined experiments after pooling all data according to IOP and MAP values. A correlation between ONHBF and MAP was found at IOPs 25 mm Hg (P<0.001), but not at IOPs>25 mm Hg (P=0.79). Optic nerve head blood flow and IOP were significantly correlated (P<0.001), and ONHBF was only slightly dependent on MAP. The data of the present study indicate a complex regulation of ONHBF during combined changes in MAP and IOP. Our results may be compatible with myogenic mechanisms underlying autoregulation, and indicate better ONHBF regulation during an increase in MAP than during an increase in IOP.

Measurement of tear film thickness using ultrahigh-resolution optical coherence tomography.

PURPOSE: To visualize the precorneal tear film with ultrahigh-resolution spectral domain optical coherence tomography, enabling quantification of tear film thickness in healthy subjects. METHODS: A custom-built spectral domain optical coherence tomography system comprising a broadband titanium:sapphire laser operating at 800 nm and a high-speed charge coupled device (CCD) camera with a read-out rate of 47 kHz was used for measurement of precorneal tear film thickness. The system provides a theoretical axial resolution of 1.2 µm in tissue. The signal-to-noise ratio close to the zero delay was measured with 94 dB. A total of 26 healthy subjects were included in this study. Measurement was started immediately after blinking and averaged over a period of 1 second. In a subset of eight healthy subjects, the reproducibility of the approach was studied by measuring the tear film thickness every 10 minutes over 1 hour. RESULTS: The average central tear film thickness of the measured population was 4.79 ± 0.88 µm. Reproducibility was very high, with an intraclass correlation coefficient of 0.97. A breakup of the tear film was observed in one subject after 14 seconds. CONCLUSIONS: Our data indicate that the human precorneal tear film can be measured with excellent reproducibility using ultrahigh-resolution optical coherence tomography. This technique may be a valuable tool in the management of dry eye syndrome.

Alterations of choroidal blood flow regulation in young healthy subjects with complement factor H polymorphism.

A common polymorphism in the complement factor H gene (rs1061170, Y402H) is associated with a high risk of age-related macular degeneration (AMD). In the present study we hypothesized that healthy young subjects homozygous for the high-risk haplotype (CC) show abnormal choroidal blood flow (ChBF) regulation decades before potentially developing the disease. A total of 100 healthy young subjects were included in the present study, of which 4 subjects were excluded due to problems with genotyping or blood flow measurements. ChBF was measured continuously using laser Doppler flowmetry while the subjects performed isometric exercise (squatting) for 6 minutes. The increase in ChBF was less pronounced than the response in ocular perfusion pressure (OPP), indicating for some degree of choroidal blood flow regulation. Eighteen subjects were homozygous for C, 47 subjects were homozygous for T and 31 subjects were heterozygous (CT). The increase in OPP during isometric exercise was not different between groups. By contrast the increase in ChBF was more pronounced in subjects homozygous for the high risk C allele (p = 0.041). This was also evident from the pressure/flow relationship, where the increase in ChBF in homozygous C carriers started at lower OPPs as compared to the other groups. Our data indicate that the regulation of ChBF is abnormal in rs1061170 CC carriers. So far this polymorphism has been linked to age related macular degeneration (AMD) mainly via inflammatory pathways associated with the complement system dysfunction. Our results indicate that it could also be related to vascular factors that have been implicated in AMD pathogenesis.

Role of nitric oxide in optic nerve head blood flow regulation during isometric exercise in healthy humans.

PURPOSE: We determined whether administration of a nitric oxide synthase (NOS) inhibitor alters optic nerve head blood flow (ONHBF) regulation during isometric exercise in healthy subjects. METHODS: Our study was done in a randomized, placebo-controlled, double-masked, three-way crossover design. A total of 18 healthy subjects was randomized to receive either placebo, phenylephrine, or an inhibitor of NOS (L-NMMA) on three different study days. ONHBF was measured with laser Doppler flowmetry while the study participants performed isometric exercise (squatting). This was done before drug administration and during infusion of the study drugs. Mean arterial pressure (MAP) and IOP were measured noninvasively, and ocular perfusion pressure (OPP) was calculated as 2/3 MAP - IOP. RESULTS: The response in ONHBF to isometric exercise was less pronounced than the response in OPP, indicating for some autoregulatory capacity in the ONH. Administration of L-NMMA significantly decreased ONHBF at rest (P < 0.01). In contrast, inhibition of NOS did not alter the pressure-flow relationship in the ONH during an experimental increase in OPP compared to phenylephrine and placebo (P = 0.37 between groups). CONCLUSIONS: The data of our study support previous findings that ONHBF is autoregulated during an experimental increase in OPP. Nitric oxide has an important role in basal ONHBF regulation, but seems not to be involved in the autoregulatory response during an increase in OPP induced by isometric exercise. (ClinicalTrials.gov number, NCT00806741.).

Measurement of retinal oxygen saturation in patients with chronic obstructive pulmonary disease.

PURPOSE: There is growing evidence that disturbances in retinal oxygenation may trigger ocular diseases. New instruments allow for the noninvasive measurement of retinal oxygen saturation in humans. The present study was designed to investigate the retinal oxygen saturation in patients with chronic obstructive pulmonary disease (COPD). This was also done in an effort to test the validity of retinal oxygenation measurements with a retinal vessel analyzer. METHODS: In all, 16 patients with severe COPD grade 4 who were on long-term oxygen treatment were included in the study. For each patient two identical study days were scheduled. Measurements of retinal arterial and venous oxygen saturation were done using a commercially available instrument for retinal oxygen analysis. Peripheral arterial oxygen saturation values were analyzed with pulse oximetry and via a capillary blood sample drawn from the earlobe. Measurements were performed during oxygen treatment and during a period without oxygen supplementation. Analysis of all images for retinal oxygen saturation quantification was done by a masked investigator. Analysis was done using Pearson's correlation and a multivariate regression model. RESULTS: Arterial and venous retinal oxygen saturation decreased significantly after the cessation of the oxygen therapy. The arteriovenous oxygen difference was unchanged while breathing ambient air or pure oxygen-enriched air. With both Pearson's correlation and the multivariate model, we found significant positive correlation coefficients between retinal arterial and peripheral arterial oxygen saturation as assessed with pulse oximetry as well as between retinal arterial and peripheral arterial oxygen saturation measured in blood samples. The change of oxygen saturation after discontinuation of oxygen supplementation showed a good correlation between retinal arterial oxygen saturation and peripheral arterial oxygen saturation (r = 0.53, P < 0.05). Reproducibility on the two study days was high. DISCUSSION: The present study shows a good correlation between retinal arterial and peripheral arterial oxygen saturation indicating good validity of the technique. (ClinicalTrials.gov number, NCT00999024.).

Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes.

PURPOSE: A variety of studies have shown that flicker-induced vasodilatation is reduced in patients with diabetes. It is, however, unclear whether reduced neural activity or abnormal neurovascular coupling is the reason for this phenomenon. In the present study, we hypothesized that retinal neurovascular dysfunction precedes neural dysfunction in patients with early type 1 diabetes. METHODS: In the present study, 50 patients with type 1 diabetes without retinopathy and 50 healthy age- and sex-matched control subjects were included. The retinal vascular response to flicker stimulation was measured using the dynamic Retinal Vessel Analyzer. In addition, the response in retinal blood velocity to flicker stimulation as assessed with laser Doppler velocimetry was studied in a subgroup of patients. Pattern electroretinography (ERG) was used to measure neural retinal function. RESULTS: The flicker responses of both retinal arteries and veins were significantly reduced in patients with diabetes (veins in the diabetic group: 3.5 ± 2.3% versus healthy control group: 4.6 ± 2.0%; P = 0.022 between groups, whereas arteries in the diabetic group: 2.0 ± 2.7% versus healthy control group: 3.8 ± 1.7%; P < 0.001 between groups). Likewise, the response of retinal blood velocity was reduced in patients with diabetes, although adequate readings could only be obtained in a subgroup of subjects (diabetic group [n = 22]: 19 ± 7%; healthy control group [n = 24]: 43 ± 19% P < 0.001 between groups). The parameters of pattern ERG were not different between the two groups. CONCLUSIONS: The study confirms that flicker responses are reduced early in patients with type 1 diabetes. This is seen before alterations in pattern ERG indicating abnormal neurovascular coupling.

Role of endothelin-A receptors in optic nerve head red cell flux regulation during isometric exercise in healthy humans.

Endothelin-1 (ET-1) is an important regulator of vascular tone in the eye. It appears to play a role in ocular disease because of its strong vasoconstrictor action, its role in intraocular pressure homeostasis, and its neurotoxic potential. We have previously shown that ET-1 is involved in choroidal red cell flux (RCF) regulation during isometric exercise in healthy humans. In the present study we hypothesized that ET-1 also plays a role in optic nerve head (ONH) RCF regulation during isometric exercise. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, two-way crossover study in 15 healthy volunteers. Subjects were randomized to receive intravenous infusions of the specific endothelin type A receptor antagonist BQ-123 and placebo on two different study days. During these infusion periods, subjects performed squatting for 6 min to increase ocular perfusion pressure (OPP). ONH RCF was assessed with laser-Doppler flowmetry, and OPP was calculated from mean arterial pressure and intraocular pressure. BQ-123 did not change OPP or ONH RCF at baseline. The relative increase in OPP during isometric exercise was comparable between both groups (between 84 and 88%, P = 0.76 between groups; P < 0.001 vs. baseline). Isometric exercise increased ONH RCF during placebo and BQ-123, but the increase was more pronounced when the endothelin type-A receptor antagonist was administered (placebo, 27.3 ± 5.4%; and BQ-123, 39.2 ± 4.4%; P = 0.007 between groups). The present data indicate that ET-1 regulates red cell flux in the ONH beyond the autoregulatory range.

Effects of orally administered moxaverine on ocular blood flow in healthy subjects.

BACKGROUND: To investigate the effect of orally administered moxaverine (Kollateral forte®) on ocular blood flow in young healthy subjects. METHODS: Sixteen healthy subjects (eight male/eight female) aged between 20 and 32 years were included in this placebo-controlled, double-masked, two-way crossover study. Volunteers received 900 mg moxaverine-hydrochloride administered orally in three equal doses or placebo identical in appearance on 2 study days. Outcome variables were measured at baseline and 5 h after first drug administration. Laser Doppler flowmetry was used to assess choroidal and optic nerve head blood flow. Blood velocities in the retrobulbar vessels were measured with color Doppler imaging. RESULTS: Neither moxaverine nor placebo changed mean arterial pressure or intraocular pressure. Neither moxaverine nor placebo had an effect on choroidal (moxaverine: by 9.5 ± 17.2 %, placebo 3.8 ± 18.8 %, p = 0.54 between groups) or optic nerve head blood flow (moxaverine: 4.8 ± 10.4 %, placebo: 1.8 ± 10.9 %, p = 0.52 between groups). Similarly, administration of moxaverine did not change blood flow velocities or calculated resistance index in the retrobulbar vessels compared to placebo. CONCLUSION: The data of the present study indicate that orally administered moxaverine does not increase ocular blood flow. This is in contrast to previous findings, where parenteral administration of moxaverine lead to a significant increase in choroidal blood flow and blood flow velocities in the retrobulbar vessels. The reason for these differing results is unclear, but may be related to the low bioavailability after oral administration.

Comparison of macular pigment in patients with age-related macular degeneration and healthy control subjects - a study using spectral fundus reflectance.

PURPOSE: Previous studies have reported an age-dependent decline of macular pigment optical density (MPOD) as well as a relative lack of MPOD in age-related macular degeneration (AMD). Results are, however, strongly dependent on the technique used. In this study, we investigated the age dependence of MPOD using spectral fundus reflectance. In addition, we hypothesized that patients with AMD have a reduced MPOD as compared to healthy controls. METHODS: A total of 85 healthy subjects and 96 patients with AMD were included in this study. The healthy control subjects showed a wide range of ages (mean, 51.6 years; range, 21-79years). Patients with AMD were significantly older (mean, 71.2 years; range, 50-89 years). Spectral fundus reflectance of the fovea was measured in a 2.3° detection field with a custom built fundus reflectometer. Calculation of MPOD was based on a previously published fundus reflectance model. RESULTS: Patients with AMD showed a reduced MPOD (0.35 ± 0.12) as compared to the healthy control group (0.39 ± 0.12, p = 0.013 between groups). No age dependence of MPOD (r = -0.14, p = 0.19) was found in the healthy control group. In the AMD group, however, MPOD declined with age (r = -0.24, p = 0.019). CONCLUSIONS: This study indicates that MPOD is reduced in patients with AMD. In addition, the data of this study indicate that MPOD is age dependent in AMD patients, but not in healthy controls. Taken together with data indicating that lutein supplementation increases MPOD, this provides a rationale for supplementation of the macular pigments in patients with AMD, although long-term clinical outcome data are lacking.

Reproducibility of retinal vessel oxygen saturation measurements in healthy young subjects.

PURPOSE: An adequate oxygenation and perfusion is essential for the function of the inner retina. Recently, several techniques for the measurement of retinal oxygen saturation became available. We set out to evaluate reproducibility of the measurements using a modified Retinal Vessel Analyzer. METHODS: A total of 20 healthy female and male subjects aged between 18 and 35 years (22.9 ± 3.9; mean ± SD) were included. The measurement of retinal oxygen saturation with the retinal oximeter employed in this study is based on optical reflectometry using the different absorption characteristics of oxygenated and deoxygenated haemoglobin. The intraclass correlation coefficients and the coefficients of variation (CV) for test-retest, short-term as well as day-to-day measurements were calculated. RESULTS: The intraclass correlation coefficients were between 0.91 and 0.94 for retinal branch arteries and between 0.84 and 0.88 for retinal branch veins. In retinal arteries, we calculated a test-retest CV of 3.24 ± 3.18% for oxygen saturation measurements. In retinal veins, data were slightly less reproducible with a CV of 4.92 ± 3.57%. Short-term reproducibility of both measurement cycles on each study day was in the same range (CV in retinal arteries: 2.91 ± 2.42% and CV in retinal veins: 4.76 ± 3.14%). The day-to-day coefficient of variation was slightly higher (CV in retinal arteries: 3.97 ± 2.87% and CV in retinal veins: 6.18 ± 3.36%). CONCLUSION: The reproducibility of haemoglobin oxygen saturation measurements using the retinal oximeter is acceptable. Further studies on the validity of the obtained results are, however, required.

Comparison of choroidal and optic nerve head blood flow regulation during changes in ocular perfusion pressure.

PURPOSE: We compared the response of choroidal and optic nerve head blood flow (ChBF, ONHBF) in response to an increase in ocular perfusion pressure (OPP) during isometric exercise and during a decrease in OPP during an artificial increase in intraocular pressure (IOP). METHODS: We included 96 healthy subjects in our study. In 48 subjects OPP was increased by 6 minutes of squatting, and either ONHBF (n = 24) or ChBF (n = 24) was measured continuously. In 48 other healthy subjects either ONHBF (n = 24) or ChBF (n = 24) was measured continuously during a period of artificial increase in IOP using a suction cup. All blood flow measurements were done using laser Doppler flowmetry. RESULTS: During all experiments the response in blood flow was less pronounced than the response in OPP, indicating for flow regulation. During isometric exercise ChBF regulated better than ONHBF (P = 0.023). During artificial IOP increase ONHBF regulated better than ChBF (P = 0.001). Inter-individual variability in blood flow responses was high. During squatting ONHBF decreased considerably below baseline ONHBF when OPP fluctuated in 3 subjects, although OPP still was much higher than at baseline. This phenomenon was not observed in the choroid. CONCLUSIONS: Our data indicate that regulation of ChBF and ONHBF during changes in OPP is different and complex. In some subjects performing squatting, considerable ONHBF reductions were observed during OPP fluctuations, although OPP still was high. Whether this predisposes to ocular disease remains unclear.

Short- and mid-term repeatability of macular pigment optical density measurements using spectral fundus reflectance.

BACKGROUND: Several methods have been proposed for measuring macular pigment optical density (MPOD). To date, none of the realized techniques can be considered as "gold standard". A key issue for the clinical applicability of a method is its repeatability. In this study, we investigated short- and mid-term repeatability of MPOD measurements using reflectometry. METHODS: A total of 12 healthy young subjects were measured 5 times on 5 consecutive days. Repeatability over 6 months was investigated in patients with AMD. The data in AMD patients were taken from a recently published placebo controlled study investigating the effect of lutein supplementation on MPOD (n = 37; [1]). Four measurements over 6 months were used to calculate repeatability. Spectral fundus reflectance of the fovea was measured in a 2.3° detection field with a custom-built fundus reflectometer. Calculation of MPOD was based on a previously published fundus reflectance model. RESULTS: The coefficients of variation were 6.2 ± 2.4% and 8.0 ± 5.5% in the healthy and AMD group, respectively. Bland-Altman plots indicate that the difference between measurements at day 1 and day 5 in healthy subjects and day 1 and month 6 in AMD patients was small. The maximum deviation in MPOD in a healthy subject was 0.07 (22.6%), and 0.17 (51.5%) in a patient with AMD. CONCLUSIONS: Reflectometry provides adequate short-term and mid-term repeatability for measuring MPOD. Accordingly, the technique makes it possible to monitor MPOD in patients with AMD and to study the influence of supplementation in these subjects. In addition, the variability of the technique is small enough to allow for clinical trials with reasonable sample size.