Mahiul M. K. Muqit

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.

In Vivo Laser-Tissue Interactions and Healing Responses From 20- vs 100-Millisecond Pulse Pascal Photocoagulation Burns

OBJECTIVES To compare in vivo burn morphologic features and healing responses of Pascal 20- and 100-millisecond panretinal photocoagulation (PRP) burns in proliferative diabetic retinopathy. DESIGN Prospective randomized controlled trial with 24 eyes assigned to either 20- or 100-millisecond Pascal PRP. Fundus autofluorescence and Fourier domain optical coherence tomography (FD-OCT) were performed 1 hour and 2 and 4 weeks after treatment. Main outcome measures included burn morphologic features on FD-OCT and greatest linear diameter (GLD) of laser burns as evaluated in 6 standard Early Treatment of Diabetic Retinopathy Study photographic fields using autofluorescence. RESULTS The contemporaneous increase in autofluorescence is observed with increasing pulse duration. Differences in mean GLD between 100- and 20-millisecond burns were 63 mum at 1 hour and 198 mum at 4 weeks (P < .001 for both). At 4 weeks, all burns corresponded to defects at the junction of inner and outer segments of photoreceptors (JI/OSP) and apical retinal pigment epithelium. After 4 weeks, the GLD of 20-millisecond burns reduced significantly by 35% (P < .001), with no change in 100-millisecond burns. CONCLUSIONS All burns initially appear as equivalent square-edged, columnar foci of hyperreflectivity in the outer retina. Pascal 20-millisecond burns progressively reduce in size, and this suggests a novel healing response localized to the JI/OSP and apical retinal pigment epithelium. The higher-fluence 100-millisecond burns develop larger defects due to thermal blooming and collateral damage.

Single-session vs multiple-session pattern scanning laser panretinal photocoagulation in proliferative diabetic retinopathy: The Manchester Pascal Study.

OBJECTIVE To investigate the effects of pattern scanning laser (Pascal; OptiMedica, Santa Clara, California) multispot panretinal photocoagulation given in a single-session (SS-PRP) vs single-spot multiple-session PRP (MS-PRP) on proliferative diabetic retinopathy (PDR). METHODS Single-center, randomized clinical trial of 40 eyes. Proliferative diabetic retinopathy was treated with a 400-mum spot size in 1500 burns given either as Pascal in 20-millisecond SS-PRP or in 3 sessions (100-millisecond MS-PRP) during a 4-week period. Visual acuity, central subfield retinal thickness (CRT), and 24-2 Swedish interactive thresholding algorithm visual fields were recorded at baseline and 4 and 12 weeks. MAIN OUTCOME MEASURES Central subfield retinal thickness, mean deviation, and PDR grade at 12 weeks. RESULTS There was a significant increase in mean CRT with MS-PRP (22 mum at 4 weeks, 95% CI, -32.25 to -10.75; 20 mum at 12 weeks, 95% CI, -28.75 to -10.82; P < .001) and no significant increase in the SS-PRP group. The mean deviation increased significantly in the SS-PRP group after 4 weeks (0.73 dB, P = .048), with no significant changes in either group at other points. A positive effect on PDR was observed in 74% of eyes in the SS-PRP group vs 53% in the MS-PRP group (P = .31). Mean treatment time for SS-PRP was 5.04 minutes (SD, 1.5 minutes) compared with 59.3 (SD, 12.7 minutes) in the MS-PRP group (P < .001). CONCLUSIONS There were no adverse outcomes (CRT, visual acuity, or visual field) from using multispot SS-PRP vs single-spot MS-PRP at 12 weeks postlaser, and treatment times were significantly shorter for multispot SS-PRP. Pascal SS-PRP was as effective as MS-PRP in the treatment of PDR. APPLICATION TO CLINICAL PRACTICE Twenty-millisecond Pascal SS-PRP may be safely and rapidly performed in 1500 burns with a similar efficacy to conventional MS-PRP. TRIAL IDENTIFIER: Research and Development Office PIN R00037, Central Manchester University Hospitals Foundation Trust.

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.

Effects of conventional argon panretinal laser photocoagulation on retinal nerve fibre layer and driving visual fields in diabetic retinopathy

AimsTo determine the effects of argon green panretinal laser photocoagulation on retinal nerve fibre layer thickness, threshold visual fields, and Estermann full-binocular visual fields over time in diabetic retinopathy.MethodProspective, pilot clinical study. Time-domain optical coherence tomography (TD-OCT) of the optic nerve head and 24-2 SITA-Fast Humphrey/Estermann visual fields (HVF, EVFs) recorded at baseline, 10 weeks, and 6 months post laser. Quantitative field analysis of central 10°, 24°, and binocular visual fields.ResultsA total of 10 eye samples were subjected to uncomplicated multiple-session 100 ms panretinal laser using 2000 burns, 300-μm spot, and mean power of 136 mW (SD ±39.3). TD-OCT detected and quantified an increase in mean retinal nerve fibre layer thickness at 10 weeks (+8 μm; P<0.05) and progressive thinning at 6 months (−4 μm; P<0.05) compared with baseline. Mean threshold sensitivities, and 10° and 24° HVF improved at both time points in the majority (9 of 10 and 8 of 10) of patients. EVFs showed no significant change with treatment.ConclusionsThis pilot study shows that conventional argon laser panretinal photocoagulation may increase the retinal nerve fibre layer thickness in the short term, presumably related to laser-induced axonal injury, with progressive thinning of nerve fibre layer over the long term. The 10° and 24° visual fields improved significantly after laser with no adverse effects on the UK standard driving fields.

Spatial and Spectral Imaging of Retinal Laser Photocoagulation Burns

PURPOSE To correlate in vivo spatial and spectral morphologic changes of short- to long-pulse 532 nm Nd:YAG retinal laser lesions using Fourier-domain optical coherence tomography (FD OCT), autofluorescence (AF), fluorescein angiography (FA), and multispectral imaging. METHODS Ten eyes with treatment-naive preproliferative or proliferative diabetic retinopathy were studied. A titration grid of laser burns at 20, 100, and 200 milliseconds was applied to the nasal retina and laser fluence titrated to produce four grades of laser lesion visibility: subvisible (SV), barely visible (BV, light-gray), threshold (TH, gray-white), and suprathreshold (ST, white). The AF, FA, FD-OCT, and multispectral imaging were performed 1 week before laser, and 1 hour, 4 weeks, and 3 and 6 months post-laser. Multispectral imaging measured relative tissue oxygen concentration. RESULTS Laser burn visibility and lesion size increased in a linear relationship according to fixed fluence levels. At fixed pulse durations, there was a semilogarithmic increase in lesion size over 6 months. At 20 milliseconds, all grades of laser lesion were reduced significantly in size after 6 months: SV, 51%; BV, 54%; TH, 49%; and ST, 50% (P < 0.001), with retinal pigment epithelial proliferation and photoreceptor infilling. At 20 milliseconds, there was healing of photoreceptor inner segment/outer segment junction layers compared with 100- and 200-millisecond lesions. Significant increases in mean tissue oxygenation (range, four to six units) within the laser titration area and in oxygen concentration across the laser lesions (P < 0.01) were detected at 6 months. CONCLUSIONS For patients undergoing therapeutic laser, there may be improved tissue oxygenation, higher predictability of burn morphology, and more spatial localization of healing responses of burns at 20 milliseconds compared with longer pulse durations over time.

Non-contact ultra-widefield imaging of retinopathy of prematurity using the Optos dual wavelength scanning laser ophthalmoscope

AimsThe purpose of this report is to demonstrate that a non-contact ultra-widefield dual wavelength laser camera (Optos) is able to capture high-quality images in retinopathy of prematurity (ROP).Materials and methodsWe conducted a retrospective review of patients attending the Oxford Eye Hospital with ROP between 1 August 2012 and 16 November 2012 that underwent standard clinical assessment. Anterior segment imaging, where relevant, was performed with Retcam. Retinal imaging was then performed with Optos, using a modified ‘flying baby position’.ResultsThe Optos scanning laser ophthalmoscope was able to acquire ultra-widefield fundal images in nine ROP subjects. The images obtained show clear views of the different stages of ROP features at the posterior pole and peripheral retina. Regression of ROP features were identified, following laser and intravitreal bevacizumab treatment. Additionally, ‘skip areas’ missed by initial laser treatment could be identified in the peripheral retina.ConclusionThe Optos ultra-widefield scanning laser ophthalmoscope is capable of acquiring clinically useful high-quality images of the fundus in ROP subjects. The imaging technique could potentially be used in monitoring ROP progression and documenting ROP regression following treatment.

Pilot randomised clinical trial of Pascal TargETEd Retinal versus variable fluence PANretinal 20 ms laser in diabetic retinopathy: PETER PAN study.

Purpose To investigate the short-term effects of high-density 20-ms laser on macular thickness using Pascal-targeted retinal photocoagulation (TRP) and reduced fluence/minimally-traumatic panretinal photocoagulation (MT-PRP) compared to standard-intensity PRP (SI-PRP) in proliferative diabetic retinopathy (PDR). Methods Prospective randomised clinical trial. Treatment-naive PDR was treated with single-session 20-ms Pascal 2500 burns photocoagulation randomised to one of three treatment arms (TRP:MT-PRP:SI-PRP). Primary outcome measure was change in central retinal thickness (CRT) on OCT. Secondary outcomes at 4 and 12 weeks post-laser included: OCT peripapillary nerve fibre layer (NFL) thickness; PDR disease regression on Optos angiography; SITA-Std visual fields (VF); and, visual acuity (VA). Results 30 eyes of 24 patients were studied, ten eyes/arm. At 12 weeks, there were significant reductions in CRT after TRP (9.6 µm; 95% CI, 1.84 to 17.36; p=0.021) and MT-PRP (17.1 µm; 95% CI, 11 to 23.2; p=0.001), versus SI-PRP (+5.9 µm; 95% CI, -6.75 to 18.55; p=0.32). PDR regression was similar between groups (TRP 70%; MT-PRP 70%; SI-PRP 90%; κ=0.76). No significant changes in VA and NFL thickness developed between groups. The VF mean deviation scores increased significantly in all groups at 12 weeks ([TRP, +0.70dB; 95% CI, 0.07 to 1.48; p=0.07], [MT-PRP, +0.63dB; 95% CI, 0.12 to 1.15; p=0.02], [SI-PRP, +1.0dB; 95% CI, 0.19 to 1.74; p=0.02]). There were no laser-related ocular complications. Conclusions This pilot study reports that high-density 20-ms Pascal TRP and MT-PRP using 2500 burns did not produce increased macular thickness or any ocular adverse events during the short-term.

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

AimsTo 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.MethodsWe 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.ResultsThere 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 mm2 ablation area, moderate PDR required 3998 PRP burns and area 456 mm2, and severe PDR needed 6924 PRP laser burns (836 mm2; P<0.05).ConclusionsMultiple 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.

Barely Visible 10-Millisecond Pascal Laser Photocoagulation for Diabetic Macular Edema: Observations of Clinical Effect and Burn Localization

PURPOSE To investigate the morphologic features and clinical efficacy of barely visible Pascal (Optimedica Corporation) photocoagulation burns in diabetic macular edema (DME) using Fourier-domain optical coherence tomography (FD OCT) and fundus autofluorescence (AF). DESIGN Interventional case series. METHODS Retrospective evaluation of 10 eyes with newly diagnosed DME that underwent barely visible Pascal photocoagulation using an array of 10-microm, 10-millisecond photocoagulation burns. FD OCT and camera-based AF was performed at baseline and at 1 hour, 2 weeks, 4 weeks, and 12 weeks after laser. Changes in retinal thickening after laser treatment were measured using retinal thickness maps within the treated sector and the central foveal subfield. RESULTS At 1 hour after treatment, burns were visualized partially with clinical biomicroscopy. AF demonstrated spots lacking autofluorescence that confirmed effective laser uptake within the Pascal arrays. Sequential changes in hyperreflectivity on FD OCT correlated with morphologic alterations seen on AF. Burns became increasingly hyperautofluorescent between 2 and 4 weeks. There were significant reductions in the retinal thickness within treated sectors on FD OCT at 2 weeks (26 +/- 32 microm; P = .012) and 3 months after laser (20 +/- 21 microm; P = .02) compared with baseline. Clinical biomicroscopic reduction of DME was the most common finding in 80%. CONCLUSIONS Barely visible 10-millisecond Pascal laser seems to produce an effect at the level of the inner and outer photoreceptor segments and apical retinal pigment epithelium, with minimal axial and lateral spread of burns. FD OCT confirmed spatial localization of AF signal changes that correlated with laser burn-tissue interactions over 3 months. The technique of lower-fluence barely visible 10-millisecond laser may reduce retinal edema within affected sectors and effectively treat DME with minimization of scar formation.