In vivo measures of anterior scleral resistance in humans with rebound tonometry.

PURPOSE: To measure regional variations in anterior scleral resistance (ASR) using a ballistic rebound tonometer (RBT) and examine whether the variations are significantly affected by ethnicity and refractive error (RE). METHODS: ASR was measured using a RBT (iCare TA01) following calibration against the biomechanical properties of agarose biogels. Eight scleral regions (nasal, temporal, superior, inferior, inferior-nasal, inferior-temporal, superior-nasal and superior-temporal) were measured at locations 4mm from the limbus. Subjects were 130 young adults comprising three ethnic groups whose RE distributions [MSE (D) ± S.D.] incorporated individuals categorised as without-myopia (NM; MSE ≥ -0.50) and with-myopia (WM; MSE < -0.50); British-White (BW): 26 NM + 0.52 ± 1.15D; 22 WM -3.83 ± 2.89D]; British-South-Asian (BSA): [9 NM + 0.49 ± 1.06D; 11 WM -5.07 ± 3.76D; Hong-Kong-Chinese (HKC): [11 NM + 0.39 ± 0.66D; 49 WM -4.46 ± 2.70D]. Biometric data were compiled using cycloplegic open-field autorefraction and the Zeiss IOLMaster. Two- and three-way repeated measures analysis of variances (anovas) tested regional differences for RBT values across both refractive status and ethnicity whilst stepwise forward multiple linear regression was used as an exploratory test. RESULTS: Significant regional variations in ASR were identified for the BW, BSA and HKC (p < 0.001) individuals; superior-temporal region showed the lowest levels of resistance whilst the inferior-nasal region the highest. Compared to the BW and BSA groups, the HKC subjects displayed a significant increase in mean resistance for each respective region (p < 0.001). With the exception of the inferior region, ethnicity was found to be the chief predictor for variation in the scleral RBT values for all other regions. Mean RE group differences were insignificant. CONCLUSIONS: The novel application of RBT to the anterior sclera confirm regional variation in ASR. Greater ASR amongst the HKC group than the BW and BSA individuals suggests that ethnic differences in anterior scleral biomechanics may exist.

Does the Swedish Interactive Threshold Algorithm (SITA) accurately map visual field loss attributed to vigabatrin?

BACKGROUND: Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. METHODS: The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years ± 14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. RESULTS: SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots , defect area and defect severity. CONCLUSIONS: Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients.

Ocular biometric correlates of ciliary muscle thickness in human myopia.

PURPOSE: Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. METHODS: Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18-40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) ≥-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. RESULTS: MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. CONCLUSIONS: Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.

Dual wavelength retinal vessel oximetry - influence of fundus pigmentation.

BACKGROUND: Clinical methods examining oxygenation parameters in humans have been used in many different care settings, but concerns have been raised regarding their clinical utility when assessing people with darker skin pigmentation. While saturation values can be crucial in emergency medicine, they are equally valuable in assessing disease mechanisms and monitoring change in disease progression. Retinal pigmentation varies across individuals and hence, can impact on retinal oxygen parameters. The objective of this study was to quantify and eliminate the impact of retinal pigmentation on retinal vessel oxygen saturation parameters measured in the superficial retinal arterioles and venules. METHODS: 105 healthy individuals of varying skin colour, iris colour and heritage were included. Following a full eye exam to exclude any ocular abnormality, all participants underwent intraocular pressure, systemic blood pressure measurements and dilated dual wavelength retinal photography. Rotation matrices were employed to minimise the dependency of retinal pigmentation on arterial and venous oxygen saturation measurements determined in a concentric measurement annulus. RESULTS: Retinal oxygen saturation in venules showed a linear correlation with retinal pigmentation (y = 0.34 × x + 38.598), whereas arterial saturation followed a polynomial pattern (y = 0.0089 × x2 + 0.7499 × x + 85.073). Both arterial and venous saturation values were corrected using local fundus pigmentation. Pre-correction retinal arterial and venous oxygen saturation were 89.0% (±13.1) and 43.7% (±11.5), respectively, and post- correction values were 94.8% (±8.7) for arteries and 56.3% (±7.0) veins. CONCLUSIONS: When assessing multi-ethnic cohorts, it is important to consider the impact of pigmentation on imaging parameters and to account for it prior to clinical interpretation.

In vivo measurement of regional variation in anterior scleral resistance to Schiotz indentation.

PURPOSE: Recent studies indicate that ocular and scleral rigidity is pertinent to our understanding of glaucoma, age related macular degeneration and the development and pathogenesis of myopia. The principal method of measuring ocular rigidity is by extrapolation of data from corneal indentation tonometry (K(o) ) using Friedenwald's transformation algorithms. Using scleral indentation (Schiotz tonometry) we assess whether regional variations in resistance to indentation occur in vivo across the human anterior globe directly, with reference to the deflection of Schiotz scale readings. METHODS: Data were collected from both eyes of 26 normal young adult subjects with a range of refractive error (mean spherical equivalent ± S.D. of -1.77 D ± 3.28 D, range -10.56 to +4.38 D). Schiotz tonometry (5.5 g & 7.5 g) was performed on the cornea and four scleral quadrants; supero-temporal (ST) and -nasal (SN), infero-temporal (IT) and -nasal (IN) approximately 8 mm posterior to the limbus. RESULTS: Values of K(o) (mm(3) )(-1) were consistent with those previously reported (mean 0.0101 ± 0.0082, range 0.0019-0.0304). In regards to the sclera, significant differences (p < 0.001) were found across quadrants with indentation readings for both loads between means for the cornea and ST; ST and SN; ST and IT, ST and IN. Mean (±S.D.) scale readings for 5.5 g were: cornea 5.93 ± 1.14, ST 8.05 ± 1.58, IT 7.03 ± 1.86, SN 6.25 ± 1.10, IN 6.02 ± 1.49; and 7.5 g: cornea 9.26 ± 1.27, ST 11.56 ± 1.65, IT 10.31 ± 1.74, SN 9.91 ± 1.20, IN 9.50 ± 1.56. CONCLUSIONS: Significant regional variation was found in the resistance of the anterior sclera to indentation produced by the Schiotz tonometer.

Retinal Vessel Oxygen Saturation Measurement Protocols and Their Agreement.

Purpose: To assess agreement between different image sizes and analysis protocols for determination of retinal vessel oxygen saturation in the peripapillary retina of healthy individuals. Methods: Retinal oximetry measurements were acquired from 87 healthy volunteers using the IMEDOS Systems oxygen module. The peripapillary retinal vessels were assessed in a concentric annulus around the optic nerve head. Single and average vessel comparisons were made at different image field sizes of 30° and 50°. Comparisons between images obtained at 30° and 50° were made in a subset of 47 of the 87 individuals. Results: All subjects were normotensive and had normal intraocular pressures (9-16 mm Hg). Analyses of agreement between single vessel, averaged vessel, and between different size images were sought by Bland-Altman analyses, of which all yielded a low bias (<1% oxygen saturation). However, agreement between single vessels of consecutive images showed increased limits of agreement compared with saturation values calculated by averaging all or just the four major arcades of one image. Agreement between 30° and 50° images showed a similar bias as when comparing data obtained with the same camera angle setting but exhibited larger confidence intervals (arteries: bias = 0.21% [9.04/-8.62]%; veins: bias = 0.71% [14.82/-13.40]%). Conclusions: Averaging methods yielded the best agreement; there was little difference in average arterial and venous oxygen saturation between protocols, which analyze all vessels versus the four largest vessels. The least agreement was found for single vessel measurements and comparisons between different camera angles. Translational Relevance: Standardization of image capture protocols (same image size and undertaking a vessel averaging approach for oxygenation analysis) will enhance the detection of smaller physiological changes in eye disease.

Regulation of oxygen saturation in retinal blood vessels in response to dynamic exercise.

PURPOSE: To evaluate the impact of dynamic exercise on retinal vessel oxygen saturation in healthy individuals. METHODS: Twenty-six healthy participants underwent moderate dynamic exercise (modified Master's two-step exercise). In all subjects, intraocular pressures (IOP), systolic and diastolic blood pressures (SBP and DBP), retinal vessel calibres and retinal arterial and venous oxygen saturation were measured at baseline, immediately following exercise and 15 min postexercise. RESULTS: Moderate dynamic exercise increased SBP and DBP immediately postexercise (SBP: 116 (±13) mmHg to 150 (±21) mmHg; p < 0.001 and DBP: 69 (±10) mmHg to 74 (±10); p < 0.001), while IOP decreased by an average of 2 mmHg (baseline: 13 (±3) mmHg)) immediately postexercise (11 (±2) mmHg). Oxygen saturation in retinal arteries remained unchanged (baseline = 93 ± 8%; immediately postexercise = 94 ± 9% and 15 min postexercise = 96 ± 8%; p = 0.069), but increased in retinal veins immediately postexercise and did not return to baseline values within 15 min postexercise (baseline = 54 ± 12%; immediately postexercise = 56 ± 15%; 15 min postexercise=57 ± 12%; p = 0.036). CONCLUSION: There is a mild increase in retinal venous oxygen saturation and there is a trend towards an increase in arterial saturation in otherwise healthy individuals following dynamic exercise.

Measurement of Scleral Thickness in Humans Using Anterior Segment Optical Coherent Tomography.

Anterior segment optical coherent tomography (AS-OCT, Visante; Zeiss) is used to examine meridional variation in anterior scleral thickness (AST) and its association with refractive error, ethnicity and gender. Scleral cross-sections of 74 individuals (28 males; 46 females; aged between 18-40 years (27.7±5.3)) were sampled twice in random order in 8 meridians: [superior (S), inferior (I), nasal (N), temporal (T), superior-temporal (ST), superior-nasal (SN), inferior-temporal (IT) and inferior-nasal (IN)]. AST was measured in 1mm anterior-to-posterior increments (designated the A-P distance) from the scleral spur (SS) over a 6mm distance. Axial length and refractive error were measured with a Zeiss IOLMaster biometer and an open-view binocular Shin-Nippon autorefractor. Intra- and inter-observer variability of AST was assessed for each of the 8 meridians. Mixed repeated measures ANOVAs tested meridional and A-P distance differences in AST with refractive error, gender and ethnicity. Only right eye data were analysed. AST (mean±SD) across all meridians and A-P distances was 725±46 µm. Meridian SN was the thinnest (662±57 µm) and I the thickest (806±60 µm). Significant differences were found between all meridians (p<0.001), except S:ST, IT:IN, IT:N and IN:N. Significant differences between A-P distances were found except between SS and 6 mm and between 2 and 4 mm. AST measurements at 1mm (682±48 µm) were the thinnest and at 6mm (818±49 µm) the thickest (p<0.001); a significant interaction occurred between meridians and A-P distances (p<0.001). AST was significantly greater (p<0.001) in male subjects but no significant differences were found between refractive error or ethnicity. Significant variations in AST occur with regard to meridian and distance from the SS and may have utility in selecting optimum sites for pharmaceutical or surgical intervention.

Comparison of subjective and objective methods to determine the retinal arterio-venous ratio using fundus photography.

PURPOSE: To assess the inter and intra observer variability of subjective grading of the retinal arterio-venous ratio (AVR) using a visual grading and to compare the subjectively derived grades to an objective method using a semi-automated computer program. METHODS: Following intraocular pressure and blood pressure measurements all subjects underwent dilated fundus photography. 86 monochromatic retinal images with the optic nerve head centred (52 healthy volunteers) were obtained using a Zeiss FF450+ fundus camera. Arterio-venous ratios (AVR), central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated on three separate occasions by one single observer semi-automatically using the software VesselMap (ImedosSystems, Jena, Germany). Following the automated grading, three examiners graded the AVR visually on three separate occasions in order to assess their agreement. RESULTS: Reproducibility of the semi-automatic parameters was excellent (ICCs: 0.97 (CRAE); 0.985 (CRVE) and 0.952 (AVR)). However, visual grading of AVR showed inter grader differences as well as discrepancies between subjectively derived and objectively calculated AVR (all p<0.000001). CONCLUSION: Grader education and experience leads to inter-grader differences but more importantly, subjective grading is not capable to pick up subtle differences across healthy individuals and does not represent true AVR when compared with an objective assessment method. Technology advancements mean we no longer rely on opthalmoscopic evaluation but can capture and store fundus images with retinal cameras, enabling us to measure vessel calibre more accurately compared to visual estimation; hence it should be integrated in optometric practise for improved accuracy and reliability of clinical assessments of retinal vessel calibres.

Regional variability in visual field sensitivity during hypercapnia.

PURPOSE: Previous investigations have demonstrated a relative vascular autoregulatory inefficiency of the inferior compared to the superior retina in healthy subjects breathing increased CO(2). The purpose of this study was to determine whether the superior and inferior visual field sensitivities of healthy eyes are similarly affected during mild hypercapnia. DESIGN: Experimental study. METHODS: Visual field analysis (Humphrey Field Analyser; SITA standard 24-2 program) was carried out on one randomly selected eye of 22 subjects (mean age, 27.7 +/- 5 years) during normal room air breathing and isoxic hypercapnia. The Student paired t-tests were used to compare the visual field indices mean deviation (MD) and pattern standard deviation (PSD) for each breathing condition. A secondary, sectoral analysis of mean pointwise sensitivity was performed for each condition. In each case a P value of <.01 was considered statistically significant (Bonferroni corrected). RESULTS: Visual field MD was -0.23 +/- 0.95dB during room air breathing and -0.49 +/- 1.04dB during hypercapnia (P =.034). Sectoral pointwise mean sensitivity deteriorated by 0.46dB (P =.006) in the upper visual hemifield during hypercapnia, whereas no significant difference was observed for the lower hemifield (P =.331). CONCLUSIONS: The upper visual hemifield exhibited a significantly greater degree of deterioration in pointwise visual field mean sensitivity compared to the lower hemifield during hypercapnic conditions. This suggests that the upper visual hemifield and hence inferior retina is more susceptible to insult during hypercapnia than the superior retina in healthy individuals. A regional susceptibility of inferior retinal function to altered vascular or metabolic effects may account for the earlier and more frequent inferior nerve fibre damage associated with glaucomatous optic neuropathy.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential objective perimetry for the diagnosis and early detection of glaucomatous field defects.

PURPOSE: Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. METHODS: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively. CONCLUSIONS: The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss.

The role of hemifield sector analysis in multifocal visual evoked potential objective perimetry in the early detection of glaucomatous visual field defects.

OBJECTIVE: The purpose of this study was to examine the effectiveness of a new analysis method of mfVEP objective perimetry in the early detection of glaucomatous visual field defects compared to the gold standard technique. METHODS AND PATIENTS: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes), and glaucoma suspect patients (38 eyes). All subjects underwent two standard 24-2 visual field tests: one with the Humphrey Field Analyzer and a single mfVEP test in one session. Analysis of the mfVEP results was carried out using the new analysis protocol: the hemifield sector analysis protocol. RESULTS: Analysis of the mfVEP showed that the signal to noise ratio (SNR) difference between superior and inferior hemifields was statistically significant between the three groups (analysis of variance, P < 0.001 with a 95% confidence interval, 2.82, 2.89 for normal group; 2.25, 2.29 for glaucoma suspect group; 1.67, 1.73 for glaucoma group). The difference between superior and inferior hemifield sectors and hemi-rings was statistically significant in 11/11 pair of sectors and hemi-rings in the glaucoma patients group (t-test P < 0.001), statistically significant in 5/11 pairs of sectors and hemi-rings in the glaucoma suspect group (t-test P < 0.01), and only 1/11 pair was statistically significant (t-test P < 0.9). The sensitivity and specificity of the hemifield sector analysis protocol in detecting glaucoma was 97% and 86% respectively and 89% and 79% in glaucoma suspects. These results showed that the new analysis protocol was able to confirm existing visual field defects detected by standard perimetry, was able to differentiate between the three study groups with a clear distinction between normal patients and those with suspected glaucoma, and was able to detect early visual field changes not detected by standard perimetry. In addition, the distinction between normal and glaucoma patients was especially clear and significant using this analysis. CONCLUSION: The new hemifield sector analysis protocol used in mfVEP testing can be used to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol, it can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. The sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucomatous visual field loss. The intersector analysis protocol can detect early field changes not detected by the standard Humphrey Field Analyzer test.

Quantification of visual field loss in age-related macular degeneration.

BACKGROUND: An evaluation of standard automated perimetry (SAP) and short wavelength automated perimetry (SWAP) for the central 10-2 visual field test procedure in patients with age-related macular degeneration (AMD) is presented in order to determine methods of quantifying the central sensitivity loss in patients at various stages of AMD. METHODS: 10-2 SAP and SWAP Humphrey visual fields and stereoscopic fundus photographs were collected in 27 eyes of 27 patients with AMD and 22 eyes of 22 normal subjects. RESULTS: Mean Deviation and Pattern Standard Deviation (PSD) varied significantly with stage of disease in SAP (both p<0.001) and SWAP (both p<0.001), but post hoc analysis revealed overlap of functional values among stages. In SWAP, indices of focal loss were more sensitive to detecting differences in AMD from normal. SWAP defects were greater in depth and area than those in SAP. Central sensitivity (within 1°) changed by -3.9 and -4.9 dB per stage in SAP and SWAP, respectively. Based on defect maps, an AMD Severity Index was derived. CONCLUSIONS: Global indices of focal loss were more sensitive to detecting early stage AMD from normal. The SWAP sensitivity decline with advancing stage of AMD was greater than in SAP. A new AMD Severity Index quantifies visual field defects on a continuous scale. Although not all patients are suitable for SWAP examinations, it is of value as a tool in research studies of visual loss in AMD.

Drusen detection in retro-mode imaging by a scanning laser ophthalmoscope.

PURPOSE: The Nidek F-10 is a scanning laser ophthalmoscope that is capable of a novel fundus imaging technique, so-called 'retro-mode' imaging. The standard method of imaging drusen in age-related macular degeneration (AMD) is by fundus photography. The aim of the study was to assess drusen quantification using retro-mode imaging. METHODS: Stereoscopic fundus photographs and retro-mode images were captured in 31 eyes of 20 patients with varying stages of AMD. Two experienced masked retinal graders independently assessed images for the number and size of drusen, using purpose-designed software. Drusen were further assessed in a subset of eight patients using optical coherence tomography (OCT) imaging. RESULTS: Drusen observed by fundus photography (mean 33.5) were significantly fewer in number than subretinal deposits seen in retro-mode (mean 81.6; p < 0.001). The predominant deposit diameter was on average 5 µm smaller in retro-mode imaging than in fundus photography (p = 0.004). Agreement between graders for both types of imaging was substantial for number of deposits (weighted κ = 0.69) and moderate for size of deposits (weighted κ = 0.42). Retro-mode deposits corresponded to drusen on OCT imaging in all eight patients. CONCLUSION: The subretinal deposits detected by retro-mode imaging were consistent with the appearance of drusen on OCT imaging; however, a larger longitudinal study would be required to confirm this finding. Retro-mode imaging detected significantly more deposits than conventional colour fundus photography. Retro-mode imaging provides a rapid non-invasive technique, useful in monitoring subtle changes and progression of AMD, which may be useful in monitoring the response of drusen to future therapeutic interventions.

Altered blood vessel responses in the eye and finger in coronary artery disease.

PURPOSE: Cardiac function, such as heart rate variability, is abnormal in coronary artery disease, but its relation with the function of ocular and nail-fold blood vessels is unknown. The hypothesis was that there is abnormal retinal and peripheral microvascular endothelial function compared with large blood vessel and cardiac function. Twenty-four patients with coronary artery disease (CAD) and 30 healthy, age- and sex-matched control subjects were enrolled in the study. METHODS: Peripheral microcirculatory function was measured with continuous retinal vessel diameter assessment and nail-fold capillaroscopy. Systemic vascular function was evaluated by 24-hour blood pressure, arterial stiffness, low (LF)- and high (HF)-frequency heart rate variability, ECG monitoring, and the plasma markers von Willebrand factor (vWf) and soluble E selectin. RESULTS: Peripheral nail-fold capillary (P = 0.009) and retinal vessel (average baseline corrected flicker response [BFR]; P = 0.034) responses and reaction time in response to flicker (P = 0.016) were significantly different in patients compared with controls. Furthermore, patients demonstrated higher arterial stiffness (P = 0.005), LF and HF heart rate variability (P = 0.004, P = 0.006), and vWf level (P = 0.044), but there was no difference in soluble E selectin level (P = 0.278). In the CAD patients, LF and HF heart rate variability both correlated with average BFR (r = 0.58, P = 0.004; r = -0.6, P = 0.003, respectively). There was no such relationship in the healthy controls. CONCLUSIONS: Microcirculatory abnormalities of the retina and nail-fold vessels are present in CAD. The two indices of heart rate variability correlated with an index of ocular vessel responses. The latter may be a surrogate marker of abnormal heart rate variability in CAD.

Continuous retinal vessel diameter measurements: the future in retinal vessel assessment?

PURPOSE: To establish an alternative method, sequential and diameter response analysis (SDRA), to determine dynamic retinal vessel responses and their time course in serial stimulation compared with the established method of averaged diameter responses and standard static assessment. METHODS: SDRA focuses on individual time and diameter responses, taking into account the fluctuation in baseline diameter, providing improved insight into reaction patterns when compared with established methods as delivered by retinal vessel analyzer (RVA) software. SDRA patterns were developed with measurements from 78 healthy nonsmokers and subsequently validated in a group of 21 otherwise healthy smokers. Fundus photography and retinal vessel responses were assessed by RVA, intraocular pressure by contact tonometry, and blood pressure by sphygmomanometry. RESULTS: Compared with the RVA software method, SDRA demonstrated a marked difference in retinal vessel responses to flickering light (P < 0.05). As a validation of that finding, SDRA showed a strong relation between baseline retinal vessel diameter and subsequent dilatory response in both healthy subjects and smokers (P = 0.001). The RVA software was unable to detect this difference or to find a difference in retinal vessel arteriovenous ratio between smokers and nonsmokers (P = 0.243). However, SDRA revealed that smokers' vessels showed both an increased level of arterial baseline diameter fluctuation before flicker stimulation (P = 0.005) and an increased stiffness of retinal arterioles (P = 0.035) compared with those in nonsmokers. These differences were unrelated to intraocular pressure or systemic blood pressure. CONCLUSIONS: SDRA shows promise as a tool for the assessment of vessel physiology. Further studies are needed to explore its application in patients with vascular diseases.

Visual field severity indices demonstrate dose-dependent visual loss from vigabatrin therapy.

PURPOSE: The aims of this study were to develop an algorithm to accurately quantify Vigabatrin (VGB)-induced central visual field loss and to investigate the relationship between visual field loss and maximum daily dose, cumulative dose and duration of dose. METHODS: The sample comprised 31 patients (mean age 37.9 years; SD 14.4 years) diagnosed with epilepsy and exposed to VGB. Each participant underwent standard automated static visual field examination of the central visual field. Central visual field loss was determined using continuous scales quantifying severity in terms of area and depth of defect and additionally by symmetry of defect between the two eyes. A simultaneous multiple regression model was used to explore the relationship between these visual field parameters and the drug predictor variables. RESULTS: The regression model indicated that maximum VGB dose was the only factor to be significantly correlated with individual eye severity (right eye: p = 0.020; left eye: p = 0.012) and symmetry of visual field defect (p = 0.024). CONCLUSIONS: Maximum daily dose was the single most reliable indicator of those patients likely to exhibit visual field defects due to VGB. These findings suggest that high maximum dose is more likely to result in visual field defects than high cumulative doses or those of long duration.

Regression analysis of ranked segment parameters for optic nerve head classification: a pilot study.

PURPOSE: To determine whether curve-fitting analysis of the ranked segment distributions of topographic optic nerve head (ONH) parameters, derived using the Heidelberg Retina Tomograph (HRT), provide a more effective statistical descriptor to differentiate the normal from the glaucomatous ONH. METHODS: The sample comprised of 22 normal control subjects (mean age 66.9 years; S.D. 7.8) and 22 glaucoma patients (mean age 72.1 years; S.D. 6.9) confirmed by reproducible visual field defects on the Humphrey Field Analyser. Three 10 degree-images of the ONH were obtained using the HRT. The mean topography image was determined and the HRT software was used to calculate the rim volume, rim area to disc area ratio, normalised rim area to disc area ratio and retinal nerve fibre cross-sectional area for each patient at 10 degree-sectoral intervals. The values were ranked in descending order, and each ranked-segment curve of ordered values was fitted using the least squares method. RESULTS: There was no difference in disc area between the groups. The group mean cup-disc area ratio was significantly lower in the normal group (0.204 +/- 0.16) compared with the glaucoma group (0.533 +/- 0.083) (p < 0.001). The visual field indices, mean deviation and corrected pattern S.D., were significantly greater (p < 0.001) in the glaucoma group (-9.09 dB +/- 3.3 and 7.91 +/- 3.4, respectively) compared with the normal group (-0.15 dB +/- 0.9 and 0.95 dB +/- 0.8, respectively). Univariate linear regression provided the best overall fit to the ranked segment data. The equation parameters of the regression line manually applied to the normalised rim area-disc area and the rim area-disc area ratio data, correctly classified 100% of normal subjects and glaucoma patients. In this study sample, the regression analysis of ranked segment parameters method was more effective than conventional ranked segment analysis, in which glaucoma patients were misclassified in approximately 50% of cases. Further investigation in larger samples will enable the calculation of confidence intervals for normality. These reference standards will then need to be investigated for an independent sample to fully validate the technique. CONCLUSIONS: Using a curve-fitting approach to fit ranked segment curves retains information relating to the topographic nature of neural loss. Such methodology appears to overcome some of the deficiencies of conventional ranked segment analysis, and subject to validation in larger scale studies, may potentially be of clinical utility for detecting and monitoring glaucomatous damage.

Patients treated with vigabatrin exhibit central visual function loss.

PURPOSE: To investigate visual function in the central 10 degrees in patients who have undergone vigabatrin (VGB) antiepileptic drug (AED) therapy with the aim of identifying a clinical regimen for assessing central visual function. METHODS: The sample comprised 12 epilepsy patients (mean age, 38.6 +/- 11.7 years) who had been treated with VGB (either as monotherapy or polytherapy). A number of central visual-function tests were carried out for each eye, including high-contrast LogMAR visual acuity, short-wavelength automated perimetry (SWAP 10-2), spatial contrast sensitivity (CSV-1000), and Farnsworth-Munsell (FM) 100-hue colour discrimination. RESULTS: The group mean cumulative VGB dose was 5,086 +/- 3,245 g. The average SWAP 10-2 mean deviation (MD) for the group was -3.24 +/- 3.23 dB; 14 eyes of eight patients showed defects (range, -1.62 to -9.46 dB). The square root of the group mean total error score for FM 100-hue was 7.42 +/- 3.84; nine eyes of five patients were classified as abnormal with an unsolved colour axis suggestive of complex drug interactions. For contrast sensitivity, 15 eyes of eight patients yielded abnormal results in one or more spatial frequencies. Defects were more prominent at higher spatial frequencies. Overall, four patients had defects in all three visual-function tests, six patients had mixed defects, and two patients were normal. CONCLUSIONS: Visual-function deficits in epilepsy patients treated with VGB are present in the central 10 degrees of the retina. We recommend a battery of investigations, including SWAP 10-2 and spatial contrast sensitivity testing, to assess central visual function.