On the relationship between visual acuity and central retinal (macular) thickness after interventions for macular oedema in diabetics: a review.

PURPOSE: The aim was to compare efficacy of treatments for diabetic macular oedema (DMO) from changes in visual acuity (VA) and central macular thickness (CMT). METHODS: Peer-reviewed articles from 2004 to 2014 reporting intravitreal injections of bevacizumab (IVB), ranibizumab (IVR) or triamcinolone acetonide (IVTA) or laser photocoagulation therapy (LPT) provided data on pre-treatment (baseline) and final outcome measures. Net changes and relative changes (percentage) were assessed by linear regression analyses. RESULTS: From 88 data sets the overall net change of VA was -0.10 ± 0.12 logMAR (mean ± standard deviation), being -0.13 ± 0.11 logMAR for IVB, 0 ± 0.08 logMAR for IVR and -0.12 ± 0.08 logMAR for IVTA as compared to 0.01 ± 0.14 logMAR for LPT. For CMT, the overall net change was -103 ± 71 microns, being -108 ± 64 microns for IVB, -182 ± 73 microns for IVR, and -102 ± 57 microns for IVTA and was -49 ± 60 microns for LPT. Overall, modest correlations were found between the absolute central retinal (macular) thickness change and the VA change, and the relative changes in these measures (p < 0.001, r = 0.522 or 0.457). The predicted visual outcome from a 100 microns reduction in CMT was -0.083 logMAR units, an effect not substantially influenced by the CMT measurement method. CONCLUSIONS: Pharmacological treatment of DMO can be expected to result in a predictable decrease in CMT with an accompanying increase in VA, with the overall outcome being better than laser treatment.

Assessment of the reliability of endothelial cell-density estimates in the presence of pseudoguttata.

PURPOSE: The purpose of this work is to assess the reliability of endothelial cell-density (ECD) estimates in corneas with different severity pseudoguttata. METHODS: Specular microscopy was undertaken on grade 1, 2, or 3 pseudoguttata patients and age-matched controls aged 52-83 years. On high magnification prints of central cornea, areas of complete cells (all sides visible) and partial 'cells' (one or more sides obscured) were measured manually. Sets of 45 complete cells were selected, as well as 75 cells that were a mixture of complete and partial cells on guttate endothelia. ECD was calculated by a progressive averaging technique. RESULTS: Each group comprised 12 patients with similar range of ECD values (1,230-4,587 cells/mm(2)). Based on 40 complete cells, ECD could be estimated to within ±3.1% for grade 3 pseudoguttata versus ±2.0% for controls. If a mixture of complete and partial cells were measured, ECD could be estimated to within ±2.8% for grade 3 pseudoguttata images (n = 70 cells) and ±1.1% for controls. The estimated variability increases to substantial levels of ±20% if only ten cells were measured. No statistical differences in ECD were noted between guttate and normal endothelia if only complete cells were measured, but could be different if partial 'cells' were included. CONCLUSIONS: Providing adequate numbers of complete cells are measured and in the absence of obvious polymegathism, ECD estimates can be made to within around ±3% in the presence of typical but significant pseudoguttata.

Central corneal thickness and intraocular pressure measures in human corneas with endothelial guttata: an observational quality control study.

PURPOSE: The aim of the present study was to assess central corneal thickness (CCT) and intraocular pressure (IOP) in eyes where the corneas were affected by different degrees of severity of endothelial pseudo-guttata or guttata. METHODS: In a prospective, case series observational study, non-contact tonometry and non-contact specular microscopy (NCSM) with pachymetry for central corneal thickness measures were undertaken as routine procedures on predominantly older patients without a history of corneal problems or contact lens wear. For those showing any signs of corneal endothelial abnormalities, images of the central cornea endothelium were further processed to measure the area (as a percentage) occupied by the guttata. RESULTS: Abnormal endothelial images were obtained from 43 patients (seven with bilateral changes) with an average age of 67.5 years. Between 1.5 and 54.9 per cent of the endothelial images were affected by guttata, which were assigned grade 1 (20 eyes), grade 2 (18 eyes) or grade 3 (11 eyes). When assessed by grade, the central corneal thickness increased and the measured IOP decreased as the guttata became more numerous and confluent. Regression analyses revealed only a weak association between central corneal thickness (p = 0.044, r = 0.149) or the measured IOP (p = 0.090, r = -0.244) and the extent of the guttata (percentage). With the apparently contrasting IOP and central corneal thickness effects, no significant IOP-CCT relationship was noted (p ≥ 0.268, r ≤ 0.160). CONCLUSIONS: Where corneas have mild-to-modest non-dystrophic endothelial guttata, there may be a less predictable effect of corneal thickness on the outcome of tonometry.

Frequent spontaneous eyeblink activity associated with reduced conjunctival surface (trigeminal nerve) tactile sensitivity.

BACKGROUND: A number of recent studies have reported high spontaneous eyeblink rate (SEBR) values in apparently normal subjects, but the reasons for this are unclear. METHODS: An assessment was made of SEBR, in 60 educated adult male subjects aged between 22 and 40 years, over a period of 5 min in silence. Half of the subjects were classified as having frequent eyeblink activity. All subjects also had their corneal and conjunctival touch (tactile) sensitivity assessed with a Cochet-Bonnet aesthesiometer immediately after the video recording of SEBR. RESULTS: SEBR ranged from 4.6 to 43.5 (mean 18.6) eyeblinks/min. The SEBR was 26.8 +/- 6.0 eyeblinks/min for those with frequent eyeblink activity as compared to just 10.3 +/- 3.5 eyeblinks/min for those with normal eyeblink activity (p < 0.001). There was no difference in palpebral aperture or exposed ocular surface area between the two groups. The average central corneal sensitivity was only marginally different between the two groups (56.8 +/- 2.8 mm vs 58.5 +/- 2.3 mm) but the conjunctival threshold sensitivity was substantially different (at 23.8 +/- 4.3 mm vs 28.5 +/- 3.5 mm; p < 0.001). SEBR was inversely correlated with the conjunctival sensitivity in those with frequent eyeblink activity (p < 0.001). CONCLUSIONS: Our study provides a clue as to the mechanism of inhibition of spontaneous eyeblink activity, namely that a certain level of ocular surface (conjunctival) sensitivity is required to keep SEBR low.

Impression cytology of a case of conjunctival metaplasia associated with oral carbamazepine use?

PURPOSE: To report a case of conjunctival squamous metaplasia associated with oral carbamazepine use. METHODS: Following completion of an ocular comfort questionnaire, biomicroscopy and a phenol red thread test, impression cytology from the inter-palpebral zone (nasal) of the bulbar conjunctival surface was undertaken using a Millcell-CM filter after topical anaesthesia with oxybuprocaine 0.4%. The filter was stained with Giemsa and colour images taken at 400x magnification by light microscopy. The images were graded and also a 35 mm was prepared. From the projected image, an overlay method was used to outline the borders such that the cell and nucleus area, and the longest and shortest dimensions could be measured by planimetry. RESULTS: A male subject, added 22 years, presented with slight conjunctival injection but no substantial symptoms and only slight surface staining with fluorescein. The subject reported use of oral carbamazepine (200mg, b.d.s.). Impression cytology showed large sheets of squamous cells (grade 2-3) with few goblet cells. The average cell area was 1509 microm(2), the long:short dimension ration averaged 1.42 and the average nucleus/cytoplasm (N/C) value was just 0.092 (or 1:11.5 as a ratio). CONCLUSIONS: Since the drug has been reported to be excreted in the tear film, and with no other risk factors (such as contact lens wear, smoking or dry eye disease), the squamous metaplasia is attributed to the use of carbamazepine.

On the use of Orbscan II to assess the peripheral corneal thickness in humans: a comparison with ultrasound pachometry measures.

PURPOSE: To compare the measures of corneal thickness measurements obtained by an optical scanning slit method with those obtained by an ultrasound (US) pachometer, with special interest in the mid-peripheral (2.5 mm from centre) and peripheral (4.5 mm from centre) region of the cornea. METHODS: Three measures of corneal thickness were taken using Orbscan II and then by US pachometry (under topical anaesthesia with benoxinate 0.4%) on 24 adults, aged 20-58 years and with up to 8.5 D of myopia. The full Orbscan topography maps were used to extract single point data along the horizontal corneal meridian for the geometric centre, 2.5 mm from centre (nasal and temporal) and 4.5 mm (nasal and temporal) from centre. No correction factor was used for the Orbscan data. The same set of measures were made with the US pachometer. In all cases, the averages of three (centre) or six (mid-periphery and periphery) readings were taken as the measurements from each cornea. RESULTS: Orbscan readings on the right eyes averaged 0.576, 0.632 and 0.712 mm for central, mid-peripheral and peripheral sites with average values for emmetropic subjects (<1 DS, n = 12) being marginally higher than for myopic subjects (average - 4.00 DS, n = 12). For US pachometry, the average values were however 0.522, 0.554 and 0.606 mm. Similar results were obtained on left eyes. Combining data from both eyes also showed that the mean difference between Orbscan II and US measures was not constant across the cornea, being 0.055 +/- 0.014 mm at the centre, 0.080 +/- 0.019 mm at mid-peripheral locations and 0.107 +/- 0.046 mm at the peripheral sites. These differences persisted after application of the generally recommended acoustic factor (x0.92) to all of the Orbscan readings. CONCLUSIONS: A single acoustic factor correction cannot be applied to all corneal thickness measures made with an Orbscan II to equate the measures to those made with an US pachometer.

An assessment of the pattern of spontaneous eyeblink activity under the influence of topical ocular anaesthesia.

PURPOSE: To determine whether there is a change in the pattern of human eyeblink events under topical ocular anaesthesia. METHODS: Forty male subjects, aged between 19 and 52 years and with no significant ocular surface disease, were recruited. Their spontaneous eyeblink activity, in primary eye gaze position and in silence, was recorded for 5-min periods, before and after instillation of benoxinate 0.4% eyedrops. The surface anaesthesia was confirmed by aesthesiometry. RESULTS: The spontaneous eyeblink rate (SEBR) decreased from 9.1+/-4.0 blinks/min to an average of 5.7+/-3.3 blinks/min, with 37 subjects showing a decreased eyeblink rate under anaesthesia. Three blink patterns were observed before anaesthesia (symmetrical, J-type and I-type) and these were essentially unchanged under anaesthesia. CONCLUSIONS: These studies confirm that the SEBR is usually reduced under surface anaesthesia (so is sensitive to exogenous control) but the pattern of the eyeblink activity is unchanged (so is less sensitive to exogenous control). The removal of exogenous stimuli by anaesthesia does not shift the eyeblink pattern to a single type, so indicates endogenous control.

Visualisation of "Marx's line" along the marginal eyelid conjunctiva of human subjects with lissamine green dye.

PURPOSE: To qualitatively assess the frequency and intensity of the staining of Marx's line with lissamine green dye. METHODS: Eighty-five non-contact lens wearers, aged 18-78 years and of white (European) or Arabic origin, were assessed. The subjects had no major eye disease, although some had mild-to-moderate congestion of the main tarsal (Meibomian) glands and/or anterior blepharitis. Lissamine green dye strips were used to stain the marginal zone of the palpebral conjunctiva, and then high magnification photo slitlamp images were taken. RESULTS: A lissamine green staining line was unmistakable in 83 of the subjects, and just evident in the other two. The line extends along the entire length of the upper and lower lid margins, and the staining broadens and extends over the puncta. In most subjects, the lissamine green-stained line was posterior to the main tarsal gland orifices, but in five subjects it was distinctly anterior to the orifices. In over two-thirds of the subjects, the width of line was much less than the distance between the gland orifices, and was at a similar distance to its width from the orifices. However, in one-third of the subjects, the width of the line was around half that of the distance between the orifices or slightly greater (i.e. approximately 0.5 mm), and this feature was more commonly present in those of non-European origin. CONCLUSION: Lissamine green dye highlights a very distinct line of cells along the marginal zone, and should be a useful tool to visualise this feature. This line of cells is thought to be the natural site of contact between the eyelid margin and the surfaces of the bulbar conjunctiva and cornea.

Effect of exercise on intraocular pressure and pulsatile ocular blood flow in a young normal population.

PURPOSE: The hypotensive effect of exercise on intraocular pressure is well documented, however, little is known about the effect of exercise on pulsatile ocular blood flow. This study examines this effect and follows the recovery of intraocular pressure and pulsatile ocular blood flow after a standard exercise period. METHODS: Eighteen visually normal subjects participated in a 4-min period of bicycle ergometry. Intraocular pressure and pulsatile ocular blood flow were measured by pneumotonometry before, immediately after exercise, and at regular intervals during the recovery period. RESULTS: Intraocular pressure was found to decrease significantly with strenuous exercise and recovered gradually toward baseline over a period of 30 min. Pulsatile ocular blood flow increased significantly immediately after exercise then returned to baseline levels between 5 and 10 min after stopping exercise. CONCLUSIONS: This study confirms the hypotensive effect of exercise on intraocular pressure and shows that exercise significantly increases pulsatile ocular blood flow.

Central corneal thickness in European (white) individuals, especially children and the elderly, and assessment of its possible importance in clinical measures of intra-ocular pressure.

PURPOSE: To ascertain the impact of central corneal thickness (CCT, as assessed by pachometry) and central corneal curvature (as assessed by keratometry) on clinical measures of intra-ocular pressure (IOP, as assessed by tonometry), especially in the young and elderly. METHODS: Pachometry, keratometry and tonometry were carried out on three groups, namely children aged 5-15 years, adults aged 32-60 years, and elderly individuals aged between 61 and 82 years. For children, ultrasound pachometry was combined with non-contact tonometry (NCT), specular microscopy was used with Perkins tonometry in the adults, and ultrasound pachometry was used with Perkins tonometry for the elderly. Central corneal curvature was assessed by keratometry. RESULTS: The average CCT in children was 0.529+/-0.034 mm (n = 104, +/-S.D.), averaged 0.533+/-0.033 in adults (n=75) and 0.527+/-0.034 mm (n=91) in the elderly. Tonometry values averaged 16.7+/-2.9 mm in children, 13.0+/-3.5 mmHg in adults and 13.6+/-2.5 mm in the elderly group. Central corneal thickness values were not predictably different in relation to central corneal curvature values. Regression analyses indicated that the tonometry values were higher in both children and the elderly who had thicker corneas (and vice versa) (p < 0.003), with the measures increasing by 1.3+/-0.4 and 2.6+/-0.4 mmHg for a 10% difference in CCT in children and the elderly, respectively. For adults, no statistically significant difference in tonometry values could be demonstrated with respect to CCT (<1 mmHg for a 10% difference in CCT), and for no group were the CCT or tonometry values predictably different in relation to central comeal curvature values. CONCLUSIONS: The results of these studies, albeit relatively small scale, indicate that in young or elderly individuals with essentially normal IOP and CCT measures, the tonometry values show only small differences with respect to CCT. The slope in the observed relationship was not that different from an average of 1.5 mmHg for a 10% different in CCT, as obtained from a literature analysis over a 30-year period. The magnitude of the effect does not provide evidence that pachometry needs to be routinely performed in glaucoma screening protocols based on tonometry. Notwithstanding, the finding of higher than expected tonometry values should be further investigated, by pachometry, especially in very young children and in the elderly.