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.

A new insight into the cellular regulation of aqueous outflow: how trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm's canal endothelial cells.

AIM: To test the hypothesis that trabecular meshwork endothelial cells (TMEs) increase the permeability of Schlemm's canal endothelial cells (SCEs) by actively releasing ligands that modulate the barrier properties of SCEs. METHODS: The TMEs were first irradiated with a laser light and allowed to condition the medium, which is then added to SCEs. The treatment response is determined by both measuring SCE permeability (flow meters) and the differential expression of genes (Affymetrix chips and quantitative polymerase chain reaction (PCR)). The cytokines secreted by the treated cells were identified using ELISA and the ability of these cytokines to increase permeability is tested directly after their addition to SCEs in perfusion experiments. RESULTS: SCEs exposed to medium conditioned by the light activated TMEs (TME-cm) respond by undergoing a differential expression (DE) of 1,120 genes relative to controls. This response is intense relative to a DE of only 12 genes in lasered SCEs. The TME-cm treatment of SCEs increased the SCE permeability fourfold. The role of cytokines in these responses is supported by two findings: adding specific cytokines established to be secreted by lasered TMEs to SCEs increases permeability; and inactivating the TME-cm by boiling or diluting, abrogates these conditioned media permeability effects. CONCLUSION: These experiments show that TMEs can regulate SCE permeability and that it is likely that TMEs have a major role in the regulation of aqueous outflow. This novel TME driven cellular mechanism has important implications for the pathogenesis of glaucoma and the mechanism of action of laser trabeculoplasty. Ligands identified as regulating SCE permeability have potential use for glaucoma therapy.

Experimental ocular surgery with a high-repetition-rate erbium:YAG laser.

PURPOSE: To evaluate the performance in ocular surgery and the ocular tissue interactions resulting from increasing the maximum repetition rate of a pulsed-mode erbium:YAG laser system from 30 to 200 pulses per second. METHODS: An erbium:YAG laser was used that emitted at 2.94 microm with an output graduated from 0.2 mJ to 25 mJ and a repetition rate from 2 Hz to 200 Hz and that was equipped with a flexible optical fiber attached to various interchangeable 20-gauge endoprobes to perform ocular surgery in enucleated pig eyes. The specific maneuvers were performed in close contact in nontransmitting aqueous media and included inner retinal ablation, retinotomy, lens capsulotomy, lens ablation, iridotomy, and iridectomy. Selected tissue specimens were examined by light microscopy. RESULTS: Increasing the repetition rate to the 200-Hz range significantly improved the smoothness, continuity, and speed of all surgical maneuvers. Compared with the 30-Hz rate, substantially lower energies per pulse were efficient with the 200-Hz rate. The "sticking effect" between the tip of the probe and the target tissue at low-repetition rates, which resulted in discontinuation of the surgical maneuver, particularly during lens surgery, was eliminated with the use of high-repetition rates. Use of high-repetition rates produced a zone of residual thermal damage less than 30 microm in all ocular tissues. The histologic findings of tissue interactions were comparable to those obtained in published studies in which the same wavelength and low hertz rates were used. CONCLUSIONS: The high-repetition-rate erbium:YAG laser technology described is advantageous, compared with low-repetition-rate erbium:YAG lasers, and is applicable in a variety of ocular surgical procedures. Innovations in endoprobe design and further study will determine its role in contemporary ocular surgery.

Multicenter clinical experience using an erbium:YAG laser for vitreoretinal surgery.

PURPOSE: To evaluate the advantages, disadvantages, safety, complications, and surgical applicability of an erbium:YAG laser system for maneuvers in vitreoretinal surgery. METHODS: A prospective, consecutive trial of 68 eyes in 66 patients undergoing vitreoretinal surgery in which an erbium:YAG laser with graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and equipped with a flexible fiber optic and interchangeable 20-gauge intraocular fiber optic endoprobes was used to perform specific maneuvers, including transection, incision, and ablation of membranes, retinotomy, vessel coagulation, iridectomy, and lens tissue ablation. The patients were treated in five centers in contemporary vitreoretinal surgical settings for surgical indications, including proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and retinopathy of prematurity. RESULTS: One hundred seventy-four maneuvers were performed with an overall surgical efficacy rating of excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal membrane transection to a low of 25% for coagulation of blood vessels. Complications included retinal break or photocoagulative injury in 5% of epiretinal membrane incisions, minor bleeding from transected retinal vessels during 29% of retinotomies, and intraocular lens damage during two posterior capsulotomies. The most significant limitation was the cautious pace used during maneuvers near the retinal surface. CONCLUSION: The erbium:YAG laser is capable of versatile new approaches offering precise tissue cutting and ablation in vitreoretinal surgical maneuvers with a high degree of safety. The main limitation encountered was the slow speed of certain critical maneuvers near the retina.

Initial clinical experience with an erbium:YAG laser for vitreoretinal surgery.

PURPOSE: We tested the efficacy of an erbium:YAG laser for maneuvers in patients undergoing vitreoretinal surgery. METHODS: An erbium:YAG laser equipped with a flexible fiberoptic and interchangeable 20-gauge endoprobes of various tip configurations ranging from 100 to 365 microns was used for specific maneuvers in 13 patients referred for vitreoretinal surgery for diabetic traction detachment, proliferative vitreoretinopathy, retinal detachment with posterior break, and epimacular membrane. The following maneuvers were performed: (1) transection of elevated vitreous membranes, (2) incision of epiretinal membranes, (3) drainage and relaxing retinotomy, (4) transection of subretinal membranes, (5) noncontact ablation of epiretinal membranes in air-filled eyes, (6) ablation of lens remnants, (7) posterior capsulotomy, (8) iris surgery, and (9) retinal vascular coagulation. RESULTS: Forty-eight defined maneuvers were performed with energy levels ranging from 0.2 to 5.0 mJ and repetition rates of 2 to 30 Hz. Transection of elevated membranes, subretinal membranes, and retinotomies were easily performed. Fourteen incisions into vascularized epiretinal membranes in diabetic traction detachment surgery demonstrated a fine margin of coagulation that permitted hemostatic incision. Retinal breaks were created during one of these incisions. Lens remnant ablation, posterior capsulotomy, and iris tissue removal were successful, with a single complication consisting of damage to the posterior surface of an intraocular lens during a pars plana posterior capsulotomy accomplished by means of a side-firing probe. Epiretinal membrane ablations in air-filled eyes were effectively performed in a gradual fashion without hemorrhage. CONCLUSIONS: The erbium:YAG laser offers precise and effective tissue cutting and removal in vitreoretinal maneuvers. Further study will determine the role of this technology in vitreoretinal surgery.