Pascal panretinal laser ablation and regression analysis in proliferative diabetic retinopathy: Manchester Pascal Study Report 4.

AIMS: To quantify the 20-ms Pattern Scan Laser (Pascal) panretinal laser photocoagulation (PRP) ablation dosage required for regression of proliferative diabetic retinopathy (PDR), and to explore factors related to long-term regression. METHODS: We retrospectively studied a cohort of patients who participated in a randomised clinical trial, the Manchester Pascal Study. In all, 36 eyes of 22 patients were investigated over a follow-up period of 18 months. Primary outcome measures included visual acuity (VA) and complete PDR regression. Secondary outcomes included laser burn dosimetry, calculation of retinal PRP ablation areas, and effect of patient-related factors on disease regression. A PDR subgroup analysis was undertaken to assess all factors related to PDR regression according to disease severity. RESULTS: There were no significant changes in logMAR VA for any group over time. In total, 10 eyes (28%) regressed after a single PRP. Following top-up PRP treatment, regression rates varied according to severity: 75% for mild PDR (n=6), 67% for moderate PDR (n=14), and 43% in severe PDR (n=3). To achieve complete disease regression, mild PDR required a mean of 2187 PRP burns and 264 mm(2) ablation area, moderate PDR required 3998 PRP burns and area 456 mm(2), and severe PDR needed 6924 PRP laser burns (836 mm(2); P<0.05). CONCLUSIONS: Multiple 20-ms PRP treatments applied over time does not adversely affect visual outcomes, with favourable PDR regression rates and minimal laser burn expansion over 18 months. The average laser dosimetry and retinal ablation areas to achieve complete regression increased significantly with worsening PDR.

Pain responses of Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation: Manchester Pascal Study, MAPASS report 2.

AIMS: To evaluate pain responses following Pascal 20 ms multi-spot and 100 ms single-spot panretinal photocoagulation (PRP). METHODS: Single-centre randomised clinical trial. 40 eyes of 24 patients with treatment-naive proliferative diabetic retinopathy randomised to 20 and 100 ms PRP under topical 0.4% oxybuprocaine. A masked grader used a pain questionnaire within 1 h (numerical pain score (NPS)) and 1 month after treatment (numerical headache score (NHS)). Primary outcome measure was NPS immediately post-PRP. Secondary outcome measures were mean NHS scores and levels of photophobia reported within 4 weeks of primary PRP. RESULTS: Mean laser fluence was significantly lower using 20 ms PRP (4.8 J/cm²) compared to 100 ms PRP (11.8 J/cm²); p < 0.001). Mean NPS scores for treatment were 2.4 (2.3) (mild) for 20 ms PRP group compared to 4.9 (3.3) (moderate) in 100 ms PRP group-a significant difference (95% CI 4.3 to 0.68; p = 0.006). Mean NHS score within 1 month was 1.5 (2.7) in 20 ms PRP group compared to 3.2 (3.5) in the 100 ms PRP group (p < 0.05). The median duration of photophobia after 20 ms PRP was 3 h, and significantly less compared to 100 ms PRP after which 72 h of photophobia was reported (p < 0.001). CONCLUSIONS: Multi-spot 20 ms PRP was associated with significantly lower levels of anxiety, headache, pain and photophobia compared to 100 ms single-spot PRP treatment. Possible reasons include lower fluence, shorter-pulse duration, and spatial summation of laser nociception with multi-spot Pascal technique.

Fundus autofluorescence and Fourier-domain optical coherence tomography imaging of 10 and 20 millisecond Pascal retinal photocoagulation treatment.

AIM: To report the evolution of pattern scanning laser (Pascal) photocoagulation burns in the treatment of diabetic retinopathy, using Fourier-domain optical coherence tomography (FD-OCT) and fundus autofluorescence (AF), and to evaluate these characteristics with clinically visible alterations in outer retina (OR) and retinal pigment epithelium (RPE). METHODS: Standard red-free and colour fundus photography (FP), FD-OCT, and fundus camera-based AF were performed in 17 eyes of 11 patients following macular and panretinal photocoagulation (PRP). RESULTS: One hour following Pascal application, visibility of threshold burns on FP was incomplete. AF enabled visualisation of complete treatment arrays at 1 h, with hypoautofluorescence at sites of each laser burn. AF signals accurately correlated with localised increased optical reflectivity within the outer retina on FD-OCT. AF signals became hyperautofluorescent at 1 week, and corresponded on FD-OCT to defects at the junction of the inner and outer segments of the photoreceptors (JI/OSP) and upper surface of RPE. A 10 ms macular laser pulse produced a localised defect at the level of JI/OSP and RPE. Macular and 20 ms PRP burns did not enlarge at 1 year's and 18 months' follow-up respectively. CONCLUSIONS: We report the in vivo spatial localisation and clinical correlation of medium-pulse Pascal photocoagulation burns within outer retina and RPE, using high-resolution FD-OCT and AF. Ophthalmoscopically invisible and threshold Pascal burns may be accurately localised and mapped by AF and FD-OCT, with monitoring over time.

Exaggerated relative nasal-temporal asymmetry of macular capillary blood flow in patients with clinically significant diabetic macular oedema.

AIMS: To compare the macular capillary blood flow of patients with clinically significant diabetic macular oedema (DMO) with that of non-diabetic subjects and to determine the relation between blood flow and capillary leakage in patients with DMO. METHODS: The sample comprised 45 non-diabetic subjects (mean age 59 years) and 18 type 2 patients with clinically significant DMO (mean age 60 years). Macular capillary blood flow measurements were acquired using the Heidelberg retina flowmeter (HRF) and a 10 degrees x2.5 degrees scan field centred on the fovea. Fluorescein angiography was undertaken on each of the diabetic patients after the completion of HRF measurements. RESULTS: Temporal macular capillary blood flow was significantly lower for the patients with clinically significant DMO compared with age matched non-diabetic subjects (ANCOVA, p = 0.0011) while relative nasal-temporal asymmetry of macular capillary blood flow was significantly higher (p = 0.0125). Nasal-temporal asymmetry of macular capillary blood flow was significantly higher for the patients with DMO and capillary leakage within the scan area (two tailed t test, p = 0.0071). Macular capillary blood flow was always lower in areas of DMO and capillary leakage. CONCLUSION: Capillary blood flow was reduced in areas of DMO and capillary leakage, suggesting the presence of a localised perturbation of capillary blood flow regulation.

Correlation of a scanning laser derived oedema index and visual function following grid laser treatment for diabetic macular oedema.

AIM: To correlate change of an oedema index derived by scanning laser tomography with change of visual function in patients undergoing grid laser photocoagulation for clinically significant diabetic macular oedema (DMO). METHODS: The sample comprised 24 diabetic patients with retinal thickening within 500 micro m of the fovea. Inclusion criteria included a logMAR visual acuity of 0.25, or better. Patients were assessed twice before a single session of grid laser treatment and within 1 week of, and at 1, 2, 4, and 12 weeks after, treatment. At each visit, patients underwent logMAR visual acuity, conventional and short wavelength automated perimetry (SWAP), and scanning laser tomography. Each visual function parameter was correlated with the mean oedema index. The mean oedema index represented the z-profile signal width divided by the maximum reflectance intensity (arbitrary units). A Pearson correlation coefficient (Bonferroni corrected) was undertaken on the data set of each patient. RESULTS: 13 patients exhibited significant correlation of the mean oedema index and at least one measure of visual function for the 10 degrees x 10 degrees scan field while 10 patients correlated for the 20 degrees x 20 degrees scan field. Seven patients demonstrated correlation for both scan fields. Laser photocoagulation typically resulted in an immediate loss of perimetric sensitivity whereas the oedema index changed over a period of weeks. Localised oedema did not impact upon visual acuity or letter contrast sensitivity when situated extrafoveally. CONCLUSIONS: Correlation of change of the oedema index and of visual function following grid laser photocoagulation was not found in all patients. An absence of correlation can be explained by the localised distribution of DMO in this sample of patients, as well as by differences in the time course of change of the oedema index and visual function. The study has objectively documented change in the magnitude and distribution of DMO following grid laser treatment and has established the relation of this change to the change in visual function.

Acoustic differences between content and function words in amyotrophic lateral sclerosis.

Studies describing acoustic characteristics of speech produced by individuals with dysarthria may help to explain intelligibility deficits for these speakers. One goal of the current study was to investigate the manner and extent to which nine speakers with mild to moderate dysarthria associated with amyotrophic lateral sclerosis (ALS) and nine healthy speakers acoustically distinguished /i/, /ae/, /u/, and /a/ in content and function words. A further aim was to evaluate the relationship between impaired speech in ALS and the magnitude of acoustic differences for vowels in content and function words. Speakers read the Farm Passage at a comfortable or habitual rate. F1 and F2 midpoint frequencies were measured, and vowel space areas were calculated. Vowel durations also were measured. The magnitude of F1, F2, vowel space area, and duration differences for vowels in content and function words was not statistically different for speakers with ALS and healthy controls. In addition, with the exception of /i/ produced by some speakers with ALS, vowel duration tended to be shorter in function words. Average F1 and F2 values for function words also tended to be centralized relative to content words. Although vowel space area differences for the two speaker groups were not statistically significant, there was a tendency for the difference in vowel space area for content and function words to be smaller for speakers with ALS than for controls. Regression analyses further indicated that the magnitude of temporal differences for vowels in content and function words was a better predictor of impaired speech than the magnitude of spectral differences for vowels in content and function words. One clinical implication is that individuals with ALS may benefit from therapy techniques targeting temporal properties of the acoustic signal.

Influence of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on short-wavelength and conventional automated perimetry.

The aim of the study was to determine the effect of laser photocoagulation for clinically significant diabetic macular oedema (DMO) on macular visual function as assessed by conventional and short-wavelength automated static threshold perimetry. The sample comprised 24 patients who required laser photocoagulation for clinically significant DMO (mean age 59.75 years, range 45-75 years). One eye of each patient was selected for the study. Patients underwent conventional and short-wavelength perimetry using programme 10-2 of the Humphrey Field Analyser on two separate occasions prior to treatment and subsequently within 1 week of, and at 1, 2, 4 and 12 weeks after, treatment. The pointwise pattern deviation plot was analysed for conventional perimetry and a pointwise horizontal and vertical hemifield asymmetry analysis was derived for short-wavelength perimetry (thereby negating the influence of pre-receptoral absorption). The extent of sensitivity loss was determined by counting the number of stimulus locations with statistical probability levels of p less than 0.05. Group mean log minimum angle of resolution (logMAR) visual acuity was largely unchanged over the course of the study. Conventional perimetry showed an increase in the group mean number of abnormal contiguous stimulus locations from 2.4 (SD 4.3, range 0-14) immediately prior to treatment, to 12.4 (SD 7.8, range 0-30) within 1 week of treatment; at 3 months post-treatment, the group mean number of abnormal contiguous stimulus locations was 8.1 (SD 6.5, range 0-20). A similar but less pronounced change was found for short-wavelength perimetry. The spatial position of the post-treatment localised sensitivity loss corresponded with the area of retinal photocoagulation. Despite proven benefit in the stabilisation of visual acuity, laser photocoagulation for clinically significant DMO invariably results in a localised loss of perimetric sensitivity within 10 degrees eccentricity of the fovea. Evidence for the value of laser therapy for clinically significant DMO must be re-examined.

Short-wavelength sensitive visual field loss in patients with clinically significant diabetic macular oedema.

The aim of the study was to compare the sensitivity of short-wavelength and conventional automated static threshold perimetry for the psychophysical detection of abnormality in patients with clinically significant diabetic macular oedema. The sample comprised 24 patients with clinically significant diabetic macular oedema (mean age 59.75 years, range 45-75 years). One eye of each patient was selected. Exclusion criteria included the presence of lenticular opacity. The sensitivity of the macular visual field of each patient was determined with programme 10-2 of the Humphrey Field Analyser on two occasions, using both short-wavelength and conventional stimulus parameters; the results of the second session were analysed to minimise learning effects. A pointwise horizontal hemifield asymmetry analysis was derived for short-wavelength perimetry (thereby negating the influence of pre-receptoral absorption); the pointwise pattern deviation probability plot was analysed for conventional perimetry. Abnormality was defined as 3 or more contiguous stimulus locations with negative asymmetries (short-wavelength) or reduced sensitivity values (conventional) that resulted in a statistical probability level of p less than 0.05. The fields of 8 patients were abnormal as assessed by conventional perimetry while all were classified as abnormal using short-wavelength perimetry. In the 8 patients who exhibited both abnormal conventional and abnormal short-wavelength perimetry results, the extent of field loss was generally greater using short-wavelength perimetry. The position of the localised field loss (i.e. as distinct from field loss that was generalised across the visual field) assessed by short-wavelength perimetry corresponded with the clinical mapping of the area of diabetic macular oedema but the extent of this loss was generally greater than that suggested by clinical assessment. Short-wavelength automated perimetry offers improved sensitivity for the psychophysical detection of clinically significant diabetic macular oedema.

Scanning laser tomography Z profile signal width as an objective index of macular retinal thickening.

AIMS: (i) To evaluate the relation between retinal thickness and the Z profile signal width of a scanning laser tomographer in selected patients exhibiting clinically manifest and circumscribed macular retinal thickening; (ii) to compare the Z profile signal width values of a group of age similar normal subjects with those of the patients with macular retinal thickening; and (iii) to present the methodology underlying the Z profile signal width derivation. METHODS: Three patients with the following conditions were selected: widespread diabetic macular oedema; localised diabetic macular oedema; and macular hole. The patients were selected because they exhibited clinically manifest and circumscribed macular retinal thickening. Patients underwent fundus photography and a clinical examination which included fundus biomicroscopy. Fourteen age similar normal subjects were also assessed. The Heidelberg retina tomograph (HRT) was utilised to acquire seven topographic images of each macula. Z profile signal width data were analysed using custom software. Signal width was measured at 50% of the maximum intensity. RESULTS: For each patient with macular retinal thickening, Z profile signal width analysis (after normalisation to reduce the influence of variation in reflectance intensity between successive images) revealed a significant (p < 0.0001) localised increase of signal width which agreed with the HRT topographic analysis of retinal height, and also the clinical assessment of retinal thickness. The mean normalised Z profile signal width for the normal subjects (assessed over the whole image) ranged from 0.278 (SD 0.039) to 0.444 (0.063); these values compared with those obtained from patients in areas of macular retinal thickening of 0.761 (0.224) to 0.953 (0.194). Z profile signal width test-retest data for the patient with localised diabetic macular oedema were plus or minus 0.159 which compared with a mean signal width value of 0.761. CONCLUSION: The evidence of this study, based upon three selected patients with macular retinal thickening and 14 normal subjects, would suggest that Z profile signal width analysis offers a non-invasive, objective, topographic, and reproducible index of macular retinal thickening. Studies employing larger sample sizes are required to determine the true clinical worth of the technique.

Objective morphological assessment of macular hole surgery by scanning laser tomography.

AIM: To assess the morphological change in retinal topography using a scanning laser tomographer following macular hole surgery. To compare the results of scanning laser tomography with clinical evaluation and visual function assessment. METHODS: The sample for this pilot study comprised four eyes exhibiting different stages of macular hole formation preoperatively. Subjects were assessed preoperatively and at 1 and 3 months postoperatively. Each assessment included visual acuity, letter contrast sensitivity, clinical examination (including automated static perimetry), and scanning laser tomography. The Heidelberg retina tomograph (HRT) was used to acquire digitised scanning laser tomography images of the macula (10 degrees and 20 degrees fields). Surgery essentially comprised vitrectomy, peeling of the posterior hyaloid face, if still attached, and intraocular gas tamponade. The magnitude and significance of topographic change were determined postoperatively using the HRT topographic difference facility. RESULTS: Topographic difference analysis of the right and left eyes of case 1 showed a significant reduction in the height of the retina postoperatively. Topographic difference analysis of case 2 showed no significant change in topography. Topographic difference analysis of case 3 showed a significant increase in the height of the retina postoperatively. Scanning laser tomography agreed with clinical assessment based upon fundus biomicroscopy in three of the four eyes studied; the postoperative closure of the stage 2 macular hole (as noted by clinical assessment) proved to be too small to reach statistical significance. Scanning laser tomography agreed with the assessment of visual function in two eyes; the agreement between scanning laser tomography and visual function depends, in part, on the stage of development of the macular hole. CONCLUSION: Scanning laser tomography provides an objective evaluation of the outcome of macular hole surgery. Studies employing larger sample sizes are required to fully determine the clinical worth of the technique.

Spectral properties of fricatives in amyotrophic lateral sclerosis.

Spectral characteristics of word initial /s/ and "sh" produced by individuals with amyotrophic lateral sclerosis (ALS) and healthy controls were quantified using spectral moment analysis. Coefficients of the first four moments were used as descriptive indices of central tendency, spread of energy, shape, and peakedness. The relationship between select moment coefficients and consonant precision ratings was investigated to explore potential perceptual correlates of the acoustic measures. To examine whether spectra for ALS and healthy speakers were influenced similarly by context, first moment coefficients for three occurrences of /s/ in "some" were inspected for individual speakers. Select moment coefficients also were compared to hand-derived spectral measures for a subset of speakers. Results suggest articulatory differences in /s/ and "sh" for the present group of ALS speakers and healthy controls, as indexed by between-group differences in first moment coefficients. A linear function accounted for a significant proportion of the variance in the relationship between consonant precision ratings and the frequency difference between the first moment for /s/ and "sh". Inspection of first moment coefficients for multiple occurrences of /s/ in "some" suggests context influences the first moment in a similar manner for ALS and healthy speakers. The subanalysis comparing moment coefficients and hand-derived spectral measures revealed both similarities and differences in the manner the two measurement techniques reflect spectral shape.

The influence of speaking rate on vowel space and speech intelligibility for individuals with amyotrophic lateral sclerosis.

The relationship between speaking rate, vowel space area, and speech intelligibility was studied in a group of 9 subjects with amyotrophic lateral sclerosis (ALS) and 9 age- and gender-matched controls. Subjects read a standard passage (the Farm Passage) at three speaking rates, including HABITUAL, FAST, and SLOW. Vowel segment durations and target formant frequencies were measured at each speaking rate from select words containing the vowels /i/, /ae/, /a/, and /u/. To quantify changes in vowel space area across speaking rate, the area of the vowel quadrilateral was calculated for each speaker at each speaking rate. In addition, intelligibility estimates at each speaking rate were obtained for the dysarthric speakers. Results revealed that dysarthric speakers exhibited smaller vowel space areas and less systematic changes in vowel space as a function of speaking rate, when compared to the neurologically intact speakers. In an examination of the relationship between vowel space area and speech intelligibility, vowel space was found to account for 45% of the variance in speech intelligibility. This result suggests that vowel space area is an important component of global estimates of speech intelligibility.

Characteristics of speaking rate in the dysarthria associated with amyotrophic lateral sclerosis.

The ability to alter speaking rate was studied in a group of 9 subjects with amyotrophic lateral sclerosis (ALS) and 9 age- and gender-matched, neurologically intact controls. Subjects were instructed to speak at three different rates (i.e., habitual, twice as fast as habitual, and one-half as fast as habitual). Speaking rate, articulation rate, and pause duration and frequency were calculated. The proportional increase in speaking rate was similar between the groups; however, the dysarthric speakers slowed rate to a smaller extent. Articulation rate and pause duration and frequency covaried with speaking rate in a similar manner for both groups. There was evidence that dysarthric speakers showed a greater dependence on pause duration and frequency, as compared to articulation rate, especially when increasing rate. In addition, although it was found that the slope of the function relating phrase duration to phrase length in syllables was statistically significant for both normal and dysarthric speakers, the slope of the function was significantly more shallow for the dysarthric speakers. Perceptual judgments of speaking rate indicated that dysarthric speakers spoke faster for a given physical speaking rate. Finally, results suggested that the function relating physical to perceived speaking rate grew more rapidly for dysarthric as compared to normal speakers. Discussion focuses on the importance of these findings to rate manipulation therapies and models of speaking rate in dysarthric speech.

Kinematic, acoustic, and perceptual analyses of connected speech produced by parkinsonian and normal geriatric adults.

Acoustic and kinematic analyses, as well as perceptual evaluation, were conducted on the speech of Parkinsonian and normal geriatric adults. As a group, the Parkinsonian speakers had very limited jaw movement compared to the normal geriatrics. For opening gestures, jaw displacements and velocities produced by the Parkinsonian subjects were about half those produced by the normal geriatrics. Lower lip movement amplitude and velocity also were reduced for the Parkinsonian speakers relative to the normal geriatrics, but the magnitude of the reduction was not as great as that seen in the jaw. Lower lip closing velocities expressed as a function of movement amplitude were greater for the Parkinsonian speakers than for the normal geriatrics. This increased velocity of lower lip movement may reflect a difference in the control of lip elevation for the Parkinsonian speakers, an effect that increased with the severity of dysarthria. Acoustically, the Parkinsonian subjects had reduced durations of vocalic segments, reduced formant transitions, and increased voice onset time compared to the normal geriatrics. These effects were greater for the more severe, compared to the milder, dysarthrics and were most apparent in the more complex, vocalic gestures.

Deficits in the production of grip forces in Down syndrome.

Down syndrome (DS) and control individuals were examined as to their ability to adapt grip forces to changes in the properties of lifted objects. The DS group generated substantially greater grip forces than the controls in all tests and failed to adapt normally to changes in the frictional properties of the objects. Their greater grip forces were not due to greater slipperiness of the skin of their fingers. These results are consistent with other findings of subtle deficits in DS individuals' use of somatosensory information for controlling movement and posture.