Ian A. Cunliffe

Diurnal variation of ocular hysteresis in normal subjects: relevance in clinical context.

Background:  This study was conducted to assess the diurnal variation in ocular hysteresis, as measured by the Ocular Response Analyser to establish a relationship between diurnal hysteresis variation and diurnal intraocular pressure (IOP) variation.

A Comparison of Visual Field Progression Criteria of 3 Major Glaucoma Trials in Early Manifest Glaucoma Trial Patients

PURPOSE Three major glaucoma trials, all using the same Humphrey visual field tests, specified different criteria to define visual field progression. This article compares the performance of these criteria with a reference standard of unanimous classifications by 3 independent glaucoma experts. DESIGN Longitudinal, comparative study of diagnostic criteria. PARTICIPANTS AND CONTROLS Two hundred forty-five patients with manifest glaucoma in the Early Manifest Glaucoma Trial (EMGT). METHODS Visual field series of 1 eye of each of 245 EMGT patients were classified by 3 independent glaucoma specialists as definitely progressing, definitely nonprogressing, or neither. Field series that were classified in the first 2 categories by all 3 experts met the reference standards for the progressing and nonprogressing groups and were analyzed according to the progression criteria of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), and the EMGT. Sensitivity, specificity, time to progression, and sustainability were calculated. MAIN OUTCOME MEASURES Progression, nonprogression, sensitivity, specificity, time to progression, and sustainability. RESULTS Seventy-seven field series were definitely progressing, and 95 series were definitely nonprogressing. Among progressing eyes, 45 (58%) of 77 were identified using AGIS criteria, 58 (75%) of 77 were identified with CIGTS criteria, and 74 (96%) of 77 were identified with EMGT criteria; all comparisons of sensitivities were significant, simultaneous (P<0.001), and pairwise (P<0.01). The specificity for EMGT criteria was 89%, lower (P<0.05) than that of AGIS (98%) and CIGTS (99%) criteria. Median time to progression was considerably shorter with EMGT criteria (33 months; 95% confidence interval [CI], 30-36 months) than with AGIS (66 months; 95% CI, 57-78 months) and CIGTS (55 months; 95% CI, 48-66 months) criteria. Sustainability increased with time after progression; it averaged 79%, 84%, and 81%, respectively, for AGIS, CIGTS, and EMGT criteria during the first year after the first progression and 95%, 100%, and 93% during the fourth year after progression. CONCLUSIONS The EMGT criteria identified progression earlier and more often than AGIS and CIGTS criteria. Specificity was good for all criteria but was better with AGIS and CIGTS than with EMGT criteria. Sustainability was high for all 3 sets of criteria and best for CIGTS criteria and increased with time after progression.

Ocular response analyser to assess hysteresis and corneal resistance factor in low tension, open angle glaucoma and ocular hypertension

Purpose:  The aim of this study is to compare the hysteresis and corneal resistance factor (CRF) in normal tension glaucoma (NTG), primary open angle glaucoma (POAG) and ocular hypertension (OHT) eyes measured by the ocular response analyser (ORA).

Subjective and objective performance of the Lenstec KH-3500 "accommodative" intraocular lens

Aim: To determine whether eyes implanted with the Lenstec KH-3500 “accommodative” intraocular lenses (IOLs) have improved subjective and objective focusing performance compared to a standard monofocal IOLs. Methods: 28 participants were implanted monocularly with a KH-3500 “accommodative” IOL and 20 controls with a Softec1 IOL. Outcome measures of refraction, visual acuity, subjective amplitude of accommodation, objective accommodative stimulus response curve, aberrometry, and Scheimpflug imaging were taken at ∼3 weeks and repeated after 6 months. Results: Best corrected acuity with the KH-3500 was 0.06 (SD 0.13) logMAR at distance and 0.58 (0.20) logMAR at near. Accommodation was 0.39 (0.53) D measured objectively and 3.1 (1.6) D subjectively. Higher order aberrations were 0.87 (0.85) μm and lower order were 0.24 (0.39) μm. Posterior subcapsular light scatter was 0.95% (1.37%) greater than IOL clarity. In comparison, all control group measures were similar except objective (0.17 (0.13) D; p = 0.032) and subjective (2.0 (0.9) D; p = 0.009) amplitude of accommodation. Six months following surgery, posterior subcapsular scatter had increased (p<0.01) in the KH-3500 implanted subjects and near word acuity had decreased (p<0.05). Conclusions: The objective accommodating effects of the KH-3500 IOL appear to be limited, although the subjective and objective accommodative range is significantly increased compared to control subjects implanted with conventional IOLs. However, this “accommodative” ability of the lens appears to have decreased by 6 months post-surgery.

Effect of senescence on ocular blood flow in the retina, neuroretinal rim and lamina cribrosa, using scanning laser Doppler flowmetry.

Purpose To determine the effects of age on blood flow measurements obtained using the scanning laser Doppler flowmeter (SLDF).Method Using SLDF (Heidelberg retina flowmeter, Heidelberg Engineering, Germany) three 10° images were taken of the superior temporal retina and three further images of the superior temporal neuroretinal rim in 15 young, healthy subjects (mean age 27.9 years ± 6.2 years) and 15 mature, healthy subjects (mean age 65.2 years ± 13.7 years). In addition, measurements were taken of the lamina cribrosa in 12 of the volunteers from each subject group (mean age 27.1 ± 6.3 years and 64.8 ± 13.2 years respectively). Using a 10 × 10 pixel measurement frame, blood flow readings were obtained at a predetermined position on the retina, neuroretinal rim and lamina cribrosa. Student’s two-tailed unpaired t-tests were used to compare measures of blood flow, volume and velocity between the two subject groups (P < 0.05). In addition, linear regression analysis was used to assess the relationship between age and blood flow, volume and velocity at the retina, neuroretinal rim and lamina cribrosa.Results Retinal blood volume measured at the retina was significantly lower in the mature compared with the young subject group (P = 0.01). Mature subjects also exhibited reduced blood flow and velocity at the neuroretinal rim (P = 0.01 for both parameters) and lamina cribrosa (P = 0.008 and P = 0.01 respectively). Regression analysis revealed negative trends for all blood flow parameters in each of the anatomical areas with advancing age. Significant negative correlations were obtained for retinal blood volume (r = −0.455, P < 0.05), neuroretinal rim blood velocity (r = −0.359, P < 0.05) and lamina cribrosa blood volume (r = −0.475, P < 0.05).Conclusion Capillary blood flow in the retina, neuroretinal rim and lamina cribrosa decreases with advancing age. This may be of consequence in the progression of chronic ocular diseases such as glaucoma, and should be considered in the longitudinal determination of change in disease monitoring.

The accuracy of the inferior>superior>nasal>temporal neuroretinal rim area rule for diagnosing glaucomatous optic disc damage.

PURPOSE To determine the accuracy with which the optic disc can be diagnosed as normal or glaucomatous according to the ISNT rule, whereby, in the normal eye, the neuroretinal rim area follows the order inferior (I) > superior (S) > nasal (N) > temporal (T). DESIGN Prospective, cross-sectional, observational, case series. PARTICIPANTS Fifty-one normal individuals and 78 individuals with open-angle glaucoma exhibiting field loss (median mean deviation, -4.37 dB; interquartile range [IQR], -2.10 to -7.96 dB; median pattern standard deviation, 5.65 dB; IQR, 2.94 to 8.56 dB). The reference diagnosis was made by 2 experts on the basis of the appearance of the optic disc and of the corresponding visual field. METHODS Stereoscopic optic disc photographs, acquired for each individual, were digitized at high resolution and analyzed using a digital, quad-buffered, stereoscopic viewing system in which a Z screen was used to dissociate the images to the 2 eyes of the observer. Three expert observers, trained to fellowship standard in glaucoma, independently undertook planimetry of the neuroretinal rim and of the disc margin from 1 eye of each individual, using a cursor moving in stereoscopic space to minimize parallax errors. Software automatically calculated the neuroretinal rim area in 10°, 30°, 40°, and 90° segments. For the ISNT rule to be obeyed, the 3 Boolean comparisons of the neuroretinal rim area, I>S, S>N, and N>T, had to be true. If any of the comparisons returned false, the rule was considered not to have been obeyed. Values were compared at a precision of 0.0001 mm(2). MAIN OUTCOME MEASURES The outcome of the ISNT rule in terms of the 3 Boolean comparisons of the neuroretinal rim area was specified in terms of the sensitivity, specificity, and hence, the positive and negative likelihood ratios. RESULTS Based on the ISNT rule being obeyed for 10° segments, the positive likelihood ratio among the 3 observers was 1.11 (95% confidence interval [CI], 0.99-1.25), 1.07 (95% CI, 0.94-1.21), and 1.06 (95% CI, 0.96-1.18), respectively. It was similar for the other segment sizes. Variants of the rule were not appreciably better. CONCLUSIONS The ISNT rule has limited utility in the diagnosis of open-angle glaucoma.

Autonomic dysfunction in unselected and untreated primary open angle glaucoma patients: a pilot study

Purpose:  To investigate the presence of silent cardiac ischaemic episodes and the status of autonomic function in consecutive, newly diagnosed and untreated primary open‐angle glaucoma patients.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma

Aim: To identify the presence, and origin, of any “dissociating factors” inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). Methods: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for ⩾5 years (mean 78.4 months (SD 9.5), range 60–101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. Results: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. Conclusion: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Application of a local search strategy improves the detection of blood flow deficits in the neuroretinal rim of glaucoma patients using scanning laser Doppler flowmetry

BACKGROUND/AIM Blood flow measures acquired using the scanning laser Doppler flowmeter (SLDF) are known to be highly susceptible to spatial and temporal variations of physiological origin. The purpose of this study was to evaluate a local search strategy intended to overcome these intrinsic variations, thereby improving the detection of blood flow defects resulting from glaucoma. METHODS The sample consisted of one eye of each of 15 glaucoma patients (aged 69.1 (SD 6.6) years) and 15 normal subjects (aged 65.2 (13.7) years). Three 10 degree images of the superior temporal retina and three images of the superior temporal rim were acquired using the Heidelberg retina flowmeter (HRF). Standard analysis was performed using a 10 × 10 pixel frame. For the search strategy the same frame was located within a 15 × 15 pixel window and manually repositioned in order to identify the highest and lowest local values of blood flow. Students pairedt test was used to identify differences between groups for the two methods (p<0.05). RESULTS The standard strategy revealed no significant differences in blood flow measures between the subjects at either the retina or neuroretinal rim. With the search strategy there was also no difference in blood flow measures at the retina. At the neuroretinal rim, the search strategy demonstrated that the highest measured blood flow, volume, and velocity values were significantly lower for the glaucoma patients (p = 0.002, 0.02, and 0.002 respectively) while comparison of the lowest flow values showed that glaucoma patients had lower blood flow and velocity only (p = 0.023 and 0.021 respectively). CONCLUSIONS Glaucoma patients exhibit reduced ocular blood flow at the neuroretinal rim, which seems to affect high velocity flow more profoundly than low velocity flow. When analysing perfusion images a local search strategy is recommend to identify the highest local blood flow values in order to optimise the ability to differentiate between subject groups.

Transient cardiac ischaemia and abnormal variations in systemic blood pressure in unselected primary open angle glaucoma patients

Purpose:  To investigate the relationship between the occurrence of transient cardiac ischaemic episodes and variations in the ambulatory 24‐h blood pressure and heart rate measurements in a group of unselected glaucoma patients.