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.

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.

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.

Pregnancy after vitrectomy for proliferative diabetic retinopathy.

A 26-year-old female with insulin-dependent diabetes of 16 years duration had a vitrectomy for a dense non-resolving vitreous haemorrhage. Two months later she became pregnant. She delivered a healthy baby and despite the known adverse effects of pregnancy on retinopathy no deterioration occurred in visual acuity or in retinal appearance.

Metal binding by intestinal mucus.

Electron probe microanalysis offers distinct advantages for the study of intestinal mucus. This technique permits analysis of metal binding in situ, requires only a small amount of tissue, allows several experiments to be performed with one animal, and can resolve variations in binding that may occur in different portions of the intestine. We have used electron probe microanalysis to examine the metal binding capacity of intestinal mucus in situ. We have exposed portions of excised intestine to various concentrations of several metals, rapidly frozen the tissue and freeze dried it. After anhydrous embedding, thick sections were cut and analyzed on silicon discs or carbon coated copper grids. Qualitative analysis shows two distinctive patterns of distribution. The results of this work show clearly that at least three divalent cations are bound by mucus, that mucus exhibits different affinities for different metals, and that binding of metals is not uniform throughout mucus.

Biogenesis of intranuclear lead-protein inclusions in mouse kidney.

A single dose of lead (5 mug/g body weight), given as lead acetate by intracardiac injection, produces, within 8 hours, characteristic fibrillar intranuclear and intracytoplasmic inclusions in proximal tubular epithelial cells in mouse kidneys; after a dose of 40 mug/g body weight, such inclusion appeared within 6 hours. Their development was completely prevented by cycloheximide (one or more intraperitoneal injections of 20 mug/g body weight). The development of intranuclear inclusions was also noted in tubular epithelial cells explanted from normal mice and grown in vitro for 15 hours in a medium containing 20 mug lead/ml. Thus, the development of the characteristic fibrillar inclusion bodies depends upon de novo synthesis of inclusion body protein, induced by lead.