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Title
Language
Date
 
Details
Source
Author(s)
Nanosecond laser treatment for age-related macular degeneration does not induce focal vision loss or new vessel growth in the retina.
English
2018

Purpose: Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD); however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice.

Methods: Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15–0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and
suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR.

Results: Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch’s membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium–derived factor, an antiangiogenic factor, was upregulated.

Conclusion: In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch’s membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when
used in a subthreshold manner.

Details Vessey KA, Ho T, Jobling AI, et al. Nanosecond laser treatment for age-related macular degeneration does not induce focal vision loss or new vessel growth in the retina. Invest Ophthalmol Vis Sci. 2018;59:731–745. DOI: 10.1167/iovs.17-23098.
Source Invest Ophthalmol Vis Sci.
Author(s) Vessey KA, Ho T, Jobling AI, et al.
Prophylactic laser in age-related macular degeneration: the past, the present and the future.
English
2018

Abstract: The presence of drusen in the posterior eye is a hallmark feature of the early stages of age-related macular degeneration and their size is an indicator of risk of progression to vision-threatening forms of the disease. Since the initial observations that laser treatment can resolve drusen, there has been great interest in whether laser treatment can be used to reduce the progression of age-related macular degeneration. In this article, we review the development of lasers for the treatment of those with age-related macular degeneration. We provide an overview of the clinical trial results that demonstrated drusen resolution but that had mixed effects on progression of disease. In addition, we provide a summary of the recent developments in pulsed lasers that are designed to reduce the energy applied to the posterior eye to provide the therapeutic effects of conventional continuous wave lasers while reducing the secondary tissue effects.

Details Findlay Q, Jobling AI, Vessey KA, et al. Prophylactic laser in age-related macular degeneration: the past, the present and the future. Eye. 2018;32:972–980. DOI: 10.1038/s41433-018-0035-1.
Source Eye.
Author(s) Findlay Q, Jobling AI, Vessey KA, et al.
Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration.
English
2017

Purpose: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is an investigation of the safety and efficacy of subthreshold nanosecond laser treatment to slow the progression of intermediate age-related macular degeneration (AMD). This report presents the novel study design and baseline characteristics.

Methods: Design: Multicenter, double-masked, randomized controlled, medical device feasibility clinical trial.
Participants: Persons with bilateral drusen > 125 m m within 1500 m m of the fovea, monocular best-corrected visual acuity (BCVA) 20/40, and microperimetric retinal ensitivity of < 25 decibels (dB) in at least 1 location within central 6 in 1 eye. Signs of late AMD; choroidal neovascularization or geographic atrophy, or anatomic end points de fi ned on multimodal imaging (MMI) as fundus auto fl uorescence-de fi ned atrophy, spectral-domain optical coherence tomography (SD-OCT) e de fi ned atrophy, or nascent GA excluded
participation.
Methods: Participants were randomized to nanosecond or sham laser treatment. Twelve laser or sham spots
are applied to the macular region of the study eye. Participants are reviewed in visits every 6 months with
functional testing and MMI for 36 months and are re-treated at each visit (until 30 months) if an end point is not
reached in the study eye.
Main Outcome Measures: Progression to late AMD or MMI-de fi ned anatomic end points in the study eye.

Results: A total of 292 participants across 6 centers were enrolled, with 145 participants randomized to arm 1 and 147 participants randomized to arm 2. Population characteristics at baseline were as follows: median age 70 years, 73% female, 90% Anglo-Saxon, and 3% current smokers. Baseline ocular characteristics of the study eyes were BCVA of 83 letters (20/25); low luminance visual acuity (LLVA) of 68 letters (20/50); hyperpigmentation, 33%; reticular pseudodrusen, 23%; square root drusen area (SD-OCT), 0.77 mm; square root drusen area (color photographs), 0.92 mm; cube root drusen volume (SD-OCT), 0.26 mm; average retinal sensitivity, 26 dB; and worst point retinal sensitivity, 20 dB. Only lutein supplement use was signi fi cantly different between treatment arms.

Conclusion: The LEAD study uses novel inclusion/exclusion criteria and end points in an attempt to optimize our study design. Risk characteristics for progression to study end points are equally distributed between treatment arms.

Details Lek JJ, Brassington KH, Luu CD, et al. Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration. Ophthalmology Retina. 2017;1(3):227–239. DOI: 10.1016/j.oret.2016.12.001.
Source Ophthalmology Retina.
Author(s) Lek JJ, Brassington KH, Luu CD, et al.
Investigations into localized re-treatment of the retina with a 3-nanosecond laser.
English
2016

Purpose: Subvisual retinal lasers necessarily cause clinically invisible lesions, hence, they could intentionally or inadvertently be targeted at precisely the same or an overlapping location during repeat laser treatment. Herein, we investigated the structural integrity and cellular responses of localized re-treatment using a nanosecond laser (2RT) currently in trials for early age-related macular degeneration.

Methods: Rats were randomly assigned to one of five groups: sham, subvisual 2RT, subvisual 2RT re-treatment, visual effect 2RT, visual effect 2RT re-treatment. Re-treatment groups were lasered on days 0 and 21; single laser groups were only lasered on day 21. All rats were euthanized at day 28 and eyes were then dissected and processed for immunohistochemistry. For re-treatment, the laser was targeted at precisely the same locations on both delivery occasions. Analytical endpoints included monitoring of retinal vascular integrity overlying lesions, investigation into any potential choroidal neovascularization, assessment of the RPE, quantification of collateral injury to photoreceptors or other neuronal classes, and delineation of glial reactivity.

Results: Repeat laser administration to rats caused ostensibly identical retinal-RPE-choroid responses to those obtained in age-matched rats that received only a single application. Specifically, 7 days after treatment, RPE cells were re-populating lesion sites. No obvious consistent differences were evident between the single and repeat laser groups. Moreover, repeat laser caused no (measurable) additive injury to photoreceptors or other retinal neuronal classes from single laser treatment. In re-lasered animals, there was no increase in microglial activity overlying and adjacent to lesion sites relative to single lasered rats. Finally, there was no evidence of choroidal neovascularization after repeat laser treatment.

Conclusion: The overall results provide a measure of confidence that re-treatment of patients with 2RT should not provide any additional risk of developing visual scotomas, choroidal neovascularizations, or inflammatory events. Indeed, the collated results indicate that the metabolic and structural disruption to the RPE-retina caused by short pulse duration laser treatment is resolved within a short time frame such that re-treatment elicits a phenotype indistinguishable from single treatment.

Details Chidlow G, Plunkett M, Casson RJ, et al. Investigations into localized re-treatment of the retina with a 3-nanosecond laser. Lasers Surg. Med. 2016;48(6):602–615. DOI: 10.1002/lsm.22506.
Source Lasers Surg. Med.
Author(s) Chidlow G, Plunkett M, Casson RJ, et al.
Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.
English
2015

Purpose: Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure.

Method: Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR.

Results: In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%).

Conclusion: Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.

Details Jobling AI, Guymer RH, Vessey KA, et al. Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage. FASEB J. 2015;29(2):696–710. DOI: 10.1096/fj.14-262444.
Source FASEB J.
Author(s) Jobling AI, Guymer RH, Vessey KA, et al.
Nanosecond‐laser application in intermediate AMD: 12‐month results of fundus appearance and macular function.
English
2014

Purpose: A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported.

Method: DESIGN: Prospective non-randomised, pilot intervention study.

Results: Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 dB), seven improved sufficiently to be taken out of this high-risk category.

Conclusion: A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD.

Details Guymer RH, Brassington KH, Dimitrov P, et al. Nanosecond‐laser application in intermediate AMD: 12‐month results of fundus appearance and macular function. Clin Exp Ophthalmol. 2014;42(5):466–479. DOI: 10.1111/ceo.12247.
Source Clin Exp Ophthalmol.
Author(s) Guymer RH, Brassington KH, Dimitrov P, et al.
Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser.
English
2013

Purpose: Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). The thermal nature of this procedure, however, defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, non-thermal laser (Retinal Regeneration Therapy; 2RT) at clinically relevant energy levels.

Method: Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532nm, 100ms pulse duration) or a short-pulse (2RT; 532nm, Q-switched, 3ns pulse) laser. Settings were at visible threshold for the CW laser (12.7J/cm 2 /pulse) and at supra- and sub-visible threshold for the 2RT laser (“High”, 2RT-H, 163mJ/cm 2 /pulse; “Low”, 2RT-L, 109mJ/cm 2 /pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR and Western blotting.

Results: The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Müller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the sub-threshold setting.

Conclusion: The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.

Details Chidlow G, Shibeeb OS, Plunkett M, et al. Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser. IOVS. 2013;54(3):2319–2332. DOI: 10.1167/iovs.12-11204.
Source IOVS.
Author(s) Chidlow G, Shibeeb OS, Plunkett M, et al.
Clinical Classification of Age-related Macular Degeneration.
English
2013

Purpose: To develop a clinical classification system for age-related macular degeneration (AMD). DESIGN: Evidence-based investigation, using a modified Delphi process. PARTICIPANTS: Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist.

Method: Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. MAIN OUTCOME MEASURES: Delphi review of the 9-item set of statements resulting from the meeting.

Results: Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a 50% risk for the highest intermediate AMD risk group.

Conclusion: The proposed basic clinical classification scale seems to be of value in predicting the risk of late AMD. Incorporating consistent nomenclature into the practice patterns of all eye care providers may improve communication and patient care.

Details Ferris FL, Wilkinson CP, Bird A, et al. Clinical Classification of Age-related Macular Degeneration. Ophthalmology. 2013;120:844–851. DOI: 10.1016/j.ophtha.2012.10.036.
Source Ophthalmology.
Author(s) Ferris FL, Wilkinson CP, Bird A, et al.
Retinal Damage Profiles and Neuronal Effects of Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel 3-Nanosecond Pulse Laser.
English
2013

Purpose: To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells.

Method: Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm 2 /pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings (‘‘High,’’ 2RT-H, 163 mJ/cm 2 /pulse; ‘‘Low,’’ 2RT-L, 109 mJ/cm 2 /pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry.

Results: Both lasers caused focal loss of RPE cells with no destruction of Bruch’s membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCa within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment.

Conclusion: Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.

Details Wood JPM, Shibeeb OS, Plunkett M, et al. Retinal Damage Profiles and Neuronal Effects of Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel 3-Nanosecond Pulse Laser. IOVS. 2013;54(3):2305–2318. DOI: 10.1167/iovs.12-11203.
Source IOVS.
Author(s) Wood JPM, Shibeeb OS, Plunkett M, et al.
Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema.
English
2012








Purpose: To assess the efficacy of a new nanopulse laser, retinal regeneration therapy for the treatment of diabetic macular oedema. Design: Randomized, non-inferiority, trial. Participants: 20 eyes of 17 subjects in the retinal regeneration therapy group and 18 eyes of 14 subjects in the conventional group were analysed.

Method: The treatment group received retinal regeneration therapy laser, and the control group received photocoagulation. Main Outcome Measures: The primary outcome was the optical coherence tomography-measured change in central retinal thickness at 6 months. A secondary outcome was the change in logarithm of minimum angle of resolution visual acuity at 6 months. Non-inferiority required the one-sided 95% confidence interval of the mean retinal thickness reduction after retinal regeneration therapy to be within 35 mm of the reduction after control laser.

Results: When outliers were included in the dataset, the difference in retinal thickness reduction by analysis of covariance was 10.9 (standard deviation 17.6) mm in favour of the control laser. The difference between groups in retinal thickness reduction was 40.8 mm. If two extreme outliers were excluded, the difference was 5.6 (standard deviation 14.2) mm in favour of the retinal regeneration therapy laser, and the D optical coherence tomography was 18.5 mm. The visual acuity difference between groups was 0.059, meeting non-inferiority requirements.

Conclusion: Although retinal thickness reduction was not unambiguously non-inferior, in the short-term, retinal regeneration therapy approximates the clinical efficacy of conventional photocoagulation, stabilizing visual acuity and providing motivation for larger trials assessing retinal regeneration therapy.

Details Casson RJ, Raymond G, Newland HS, et al. Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema. Clin Exp Ophthalmol. 2012;40(6):604–610. DOI: 10.1111/j.1442-9071.2012.02756.x.
Source Clin Exp Ophthalmol.
Author(s) Casson RJ, Raymond G, Newland HS, et al.
Retina Rejuvenation Therapy for Diabetic Macula Edema. A pilot study.
English
2012

Purpose: To prospectively investigate the safety and ef fi cacy of a novel frequency-doubled nanosecond-pulsed laser with discontinuous beam energy distribution (2RT, Ellex) for the treatment of diabetic macular edema.

Method: Twenty-three consecutive patients (38 eyes) with newly diagnosed diabetic macular edema were recruited and assessed with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness measured with optical coherence tomography (OCT/scanning laser ophthalmoscope, OPKO/OTI), microperimetry, fundus photography, and fundus fluorescein angiography. Macular grid treatments were performed with 2RT laser system by 1 operator. Patients were examined with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness, microperimetry, and fundus photography at 3 weeks and 6 weeks and 3 months and 6 months. Fundus fluorescein angiography was repeated at 3 months and 6 months.

Results: Six months postoperatively, 17 patients (28 eyes) completed the study. No complications were identified after 2RT therapy. Intraoperative retinal discoloration was observed in 2 cases, fully resolved at 3 months with no permanent anatomical or functional changes. Mean logarithm of the minimum angle of resolution visual acuity improved from 20/44 at baseline to 20/27 at 6 months. The change in best-corrected visual acuity was significant ( P = 0.0190). Central macular thickness in the central 1-mm subfield, retinal exudates and vascular leakage decreased in the majority of patients at 6 months (46, 41, and 55%, respectively), although the change from baseline was not statistically significant. Microperimetry con fi rmed photoreceptor integrity and showed a trend of improvement that correlated with decreased central macular thickness.

Conclusion: For the first time, we achieved a beneficial effect on diabetic macular edema without the side effects of conventional laser therapy. The efficacy of this system in comparison with standard argon laser photocoagulation and in the treatment of other conditions affecting the retinal pigment epithelium needs further investigation.


Details Pelosini L, Hamilton R, Mohamed M, et al. Retina Rejuvenation Therapy for Diabetic Macula Edema. A pilot study. Retina. 2012;0:1–11. DOI: 10.1097/IAE.0b013e3182670fea.
Source Retina.
Author(s) Pelosini L, Hamilton R, Mohamed M, et al.
Prophylactic laser in age-related macular degeneration: the past, the present and the future.
English
2019

Details Findlay Q, Jobling AI, Vessey KA, et al. Prophylactic laser in age-related macular degeneration: the past, the present and the future. Eye. 2018.32:972–980. DOI: 10.1038/s41433-018-0035-1.
Source Eye.
Author(s) Findlay Q, Jobling AI, Vessey KA, et al.
Retina Rejuvenation Therapy for Diabetic Macula Edema. A pilot study.
English
2019

Purpose:
To prospectively investigate the safety and ef fi cacy of a novel frequency-doubled nanosecond-pulsed laser with discontinuous beam energy distribution (2RT, Ellex) for the treatment of diabetic macular edema.

Methods:
Twenty-three consecutive patients (38 eyes) with newly diagnosed diabetic macular edema were recruited and assessed with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness measured with optical coherence tomography (OCT/scanning laser ophthalmoscope, OPKO/OTI), microperimetry, fundus photography, and fundus fluorescein angiography. Macular grid treatments were performed with 2RT laser system by 1 operator. Patients were examined with logarithm of the minimum angle of resolution best-corrected visual acuity, central macular thickness, microperimetry, and fundus photography at 3 weeks and 6 weeks and 3 months and 6 months. Fundus fluorescein angiography was repeated at 3 months and 6 months.

Results:
Six months postoperatively, 17 patients (28 eyes) completed the study. No complications were identified after 2RT therapy. Intraoperative retinal discoloration was observed in 2 cases, fully resolved at 3 months with no permanent anatomical or functional changes. Mean logarithm of the minimum angle of resolution visual acuity improved from 20/44 at baseline to 20/27 at 6 months. The change in best-corrected visual acuity was significant ( P = 0.0190). Central macular thickness in the central 1-mm subfield, retinal exudates and vascular leakage decreased in the majority of patients at 6 months (46, 41, and 55%, respectively), although the change from baseline was not statistically significant. Microperimetry con fi rmed photoreceptor integrity and showed a trend of improvement that correlated with decreased central macular thickness.

Conclusion:
For the first time, we achieved a beneficial effect on diabetic macular edema without the side effects of conventional laser therapy. The efficacy of this system in comparison with standard argon laser photocoagulation and in the treatment of other conditions affecting the retinal pigment epithelium needs further investigation.

Details Pelosini L, Hamilton R, Mohamed M, et al. Retina Rejuvenation Therapy for Diabetic Macula Edema. A pilot study. Retina. 2012.0:1–11. DOI: 10.1097/IAE.0b013e3182670fea..
Source Retina.
Author(s) Pelosini L, Hamilton R, Mohamed M, et al.
Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration.
English
2019

Purpose:
The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is an investigation of the safety and efficacy of subthreshold nanosecond laser treatment to slow the progression of intermediate age-related macular degeneration (AMD). This report presents the novel study design and baseline characteristics.

Methods:
Design: Multicenter, double-masked, randomized controlled, medical device feasibility clinical trial.

Results:
A total of 292 participants across 6 centers were enrolled, with 145 participants randomized to arm 1 and 147 participants randomized to arm 2. Population characteristics at baseline were as follows: median age 70 years, 73% female, 90% Anglo-Saxon, and 3% current smokers. Baseline ocular characteristics of the study eyes were BCVA of 83 letters (20/25); low luminance visual acuity (LLVA) of 68 letters (20/50); hyperpigmentation, 33%; reticular pseudodrusen, 23%; square root drusen area (SD-OCT), 0.77 mm; square root drusen area (color photographs), 0.92 mm; cube root drusen volume (SD-OCT), 0.26 mm; average retinal sensitivity, 26 dB; and worst point retinal sensitivity, 20 dB. Only lutein supplement use was signi fi cantly different between treatment arms.

Conclusion:
The LEAD study uses novel inclusion/exclusion criteria and end points in an attempt to optimize our study design. Risk characteristics for progression to study end points are equally distributed between treatment arms.

Details Lek JJ, Brassington KH, Luu CD, et al. Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration. Ophthalmology Retina. 2017.1(3):227–239. DOI: 10.1016/j.oret.2016.12.001.
Source Ophthalmology Retina.
Author(s) Lek JJ, Brassington KH, Luu CD, et al.
Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema.
English
2019

Purpose:
To assess the efficacy of a new nanopulse laser, retinal regeneration therapy for the treatment of diabetic macular oedema. Design: Randomized, non-inferiority, trial. Participants: 20 eyes of 17 subjects in the retinal regeneration therapy group and 18 eyes of 14 subjects in the conventional group were analysed.

Methods:

The treatment group received retinal regeneration therapy laser, and the control group received photocoagulation. Main Outcome Measures: The primary outcome was the optical coherence tomography-measured change in central retinal thickness at 6 months. A secondary outcome was the change in logarithm of minimum angle of resolution visual acuity at 6 months. Non-inferiority required the one-sided 95% confidence interval of the mean retinal thickness reduction after retinal regeneration therapy to be within 35 mm of the reduction after control laser.

Results:

When outliers were included in the dataset, the difference in retinal thickness reduction by analysis of covariance was 10.9 (standard deviation 17.6) mm in favour of the control laser. The difference between groups in retinal thickness reduction was 40.8 mm. If two extreme outliers were excluded, the difference was 5.6 (standard deviation 14.2) mm in favour of the retinal regeneration therapy laser, and the D optical coherence tomography was 18.5 mm. The visual acuity difference between groups was 0.059, meeting non-inferiority requirements.

Conclusion:

Although retinal thickness reduction was not unambiguously non-inferior, in the short-term, retinal regeneration therapy approximates the clinical efficacy of conventional photocoagulation, stabilizing visual acuity and providing motivation for larger trials assessing retinal regeneration therapy.

Details Casson RJ, Raymond G, Newland HS, et al. Pilot randomized trial of a nanopulse retinal laser versus conventional photocoagulation for the treatment of diabetic macular oedema. Clin Exp Ophthalmol. 2012.40(6):604–610. DOI: 10.1111/j.1442-9071.2012.02756.x.
Source Clin Exp Ophthalmol.
Author(s) Casson RJ, Raymond G, Newland HS, et al.
Investigations into localized re-treatment of the retina with a 3-nanosecond laser.
English
2019

Purpose:
Subvisual retinal lasers necessarily cause clinically invisible lesions, hence, they could intentionally or inadvertently be targeted at precisely the same or an overlapping location during repeat laser treatment. Herein, we investigated the structural integrity and cellular responses of localized retreatment using a nanosecond laser (2RT) currently in trials for early age-related macular degeneration.

Methods:
Rats were randomly assigned to one of five groups: sham, subvisual 2RT, subvisual 2RT re-treatment, visual effect 2RT, visual effect 2RT re-treatment. Re-treatment groups were lasered on days 0 and 21; single laser groups were only lasered on day 21. All rats were euthanized at day 28 and eyes were then dissected and processed for immunohistochemistry. For re-treatment, the laser was targeted at precisely the same locations on both delivery occasions. Analytical endpoints included monitoring of retinal vascular integrity overlying lesions, investigation into any potential choroidal neovascularization, assessment of the RPE, quantification of collateral injury to photoreceptors or other neuronal classes, and delineation of glial reactivity.

Results:
Repeat laser administration to rats caused ostensibly identical retinal-RPE-choroid responses to those obtained in age-matched rats that received only a single application. Specifically, 7 days after treatment, RPE cells were re-populating lesion sites. No obvious consistent differences were evident between the single and repeat laser groups. Moreover, repeat laser caused no (measurable) additive injury to photoreceptors or other retinal neuronal classes from single laser treatment. In re-lasered animals, there was no increase in microglial activity overlying and adjacent to lesion sites relative to single lasered rats. Finally, there was no evidence of choroidal neovascularization after repeat laser treatment.

Conclusion: 
The overall results provide a measure of confidence that re-treatment of patients with 2RT should not provide any additional risk of developing visual scotomas, choroidal neovascularizations, or inflammatory events. Indeed, the collated results indicate that the metabolic and structural disruption to the RPE-retina caused by short pulse duration laser treatment is resolved within a short time frame such that re-treatment elicits a phenotype indistinguishable from single treatment.

Details Chidlow G, Plunkett M, Casson RJ, et al. Investigations into localized re-treatment of the retina with a 3-nanosecond laser. Lasers Surg. Med. 2016.48(6):602–615. DOI: 10.1002/lsm.22506.
Source Lasers Surg. Med.
Author(s) Chidlow G, Plunkett M, Casson RJ, et al.
Laser-Mediated Activation of Human Retinal Pigment Epithelial Cells and Concomitant Release of Matrix Metalloproteinases.
English
2019

Purpose:
To investigate cellular dynamics and associated matrix metalloproteinase (MMP) release patterns of human retinal pigment epithelium (RPE) cells subsequent to irradiation by nanosecond pulsed laser at energy levels below visual threshold.

Methods:
Following a stabilization period, human RPE-Bruch’s-choroid explants were irradiated with a nanosecond laser system (Q-switched, frequency doubled YAG laser, 532 nm), using a 400 lm spot size with a discontinuous energy distribution and total irradiance of 240 mJ/cm 2 , and returned to the incubator for a further 14 days. RPE cellular dynamics were assessed using confocal laser scanning, conventional microscopy, cell viability, and proliferation assays. MMPs were quantified by gelatine zymography and densitometry.

Results:

Within 4 hours of laser intervention, 47% ± 8% (mean ± SEM, n = 6) of the RPE cells within the treatment zone showed clear signs of injury. By post-treatment days 10 to 14, most of the injured beds were repopulated by migrating RPE cells from regions surrounding the lesion. Release of inactive MMP-2 was little altered over the 2-week experimental period, whereas levels of inactive MMP-9 increased 1.3-fold by day 1 to reach a 2.8-fold threshold by day 7 (n = 4; P < 0.05). However, changes in activated MMP-2 and MMP-9 were much more profound with levels increasing 6.7 ± 2.6-fold (mean ± SEM, n = 6; P < 0.001) and 4.4 ± 1.1-fold (mean ± SEM, n = 5; P <0.01), respectively, above controls at day 7 post laser.

Conclusion:

The nanosecond laser pulse modality provides an avenue for transiently increasing the RPE-mediated release of active MMP enzymes. The likely impact of this enzymatic release on the structural and functional aspects of aging Bruch’s membrane requires further evaluation.

Details Zhang JJ, Sun Y, Hussain AA, et al. Laser-Mediated Activation of Human Retinal Pigment Epithelial Cells and Concomitant Release of Matrix Metalloproteinases. IOVS. 2012.53(6):2928–2937. DOI: 10.1167/iovs.11-8585.
Source IOVS.
Author(s) Zhang JJ, Sun Y, Hussain AA, et al.
Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage.
English
2019

Purpose:
Age-related macular degeneration (AMD) is a leading cause of vision loss, characterized by drusen deposits and thickened Bruch's membrane (BM). This study details the capacity of nanosecond laser treatment to reduce drusen and thin BM while maintaining retinal structure.

Methods:
Fifty patients with AMD had a single nanosecond laser treatment session and after 2 yr, change in drusen area was compared with an untreated cohort of patients. The retinal effect of the laser was determined in human and mouse eyes using immunohistochemistry and compared with untreated eyes. In a mouse with thickened BM (ApoEnull), the effect of laser treatment was quantified using electron microscopy and quantitative PCR.

Results:
In patients with AMD, nanosecond laser treatment reduced drusen load at 2 yr. Retinal structure was not compromised in human and mouse retina after laser treatment, with only a discrete retinal pigment epithelium (RPE) injury, and limited mononuclear cell response observed. BM was thinned in the ApoEnull mouse 3 mo after treatment (ApoEnull treated 683 ± 38 nm, ApoEnull untreated 890 ± 60 nm, C57Bl6J 606 ± 43 nm), with the expression of matrix metalloproteinase-2 and -3 increased (>260%).

Conclusion:
Nanosecond laser resolved drusen independent of retinal damage and improved BM structure, suggesting this treatment has the potential to reduce AMD progression.


Details Jobling AI, Guymer RH, Vessey KA, et al. Nanosecond laser therapy reverses pathologic and molecular changes in age-related macular degeneration without retinal damage. FASEB J. 2015.29(2):696–710. DOI: 10.1096/fj.14-262444.
Source FASEB J.
Author(s) Jobling AI, Guymer RH, Vessey KA, et al.
Nanosecond Pulse Lasers for Retinal Applications.
English
2019

Purpose:
Thermal lasers are routinely used to treat certain retinal disorders although they cause collateral damage to photoreceptors. The current study evaluated a confined, non-conductive thermal, 3-nanosecond pulse laser in order to determine how to produce the greatest therapeutic range without causing collateral damage. Data were compared with that obtained from a standard thermal laser.

Methods:

Porcine ocular explants were used; apposed neuroretina was also in place for actual laser treatment. After treatment, the retina was removed and a calcein-AM assay was used to assess retinal pigmented epithelium (RPE) cell viability in the explants. Histological methods were also employed to examine lased transverse explant sections. Three nanoseconds pulse lasers with either speckle- or gaussian-beam profile were employed in the study. Comparisons were made with a 100 milliseconds continuous wave (CW) 532 nm laser. The therapeutic energy range ratio was defined as the minimum visible effect threshold (VET) versus the minimum detectable RPE kill threshold.

Results:

The 3-nanosecond lasers produced markedly lower minimum RPE kill threshold levels than the CW laser (e.g., 36 mJ/cm2 for speckle-beam and 89 mJ/cm2 for gaussian-beam profile nanosecond lasers vs. 7,958 mJ/cm2 for CW laser). VET values were also correspondingly lower for the nanosecond lasers (130 mJ/cm2 for 3 nano-seconds speckle-beam and 219 mJ/cm2 for gaussian-beam profile vs. 1,0346 mJ/cm2 for CW laser). Thus, the therapeutic range ratios obtained with the nanosecond lasers were much more favorable than that obtained by the CW laser: 3.6:1 for the speckle-beam and 2.5:1 for the gaussian-beam profile 3-nanosecond lasers versus 1.3:1 for the CW laser.

Conclusion:

Nanosecond lasers, particularly with a speckle-beam profile, provide a much wider therapeutic range of energies over which RPE treatment can be performed, without damage to the apposed retina, as compared with conventional CW lasers. These results may have important implications for the treatment of retinal disease.

Details Wood JPM, Plunkett M, Previn V, et al. Nanosecond Pulse Lasers for Retinal Applications. Lasers Surg. Med. 2011.43:499–510. DOI: 10.1002/lsm.21087.
Source Lasers Surg. Med.
Author(s) Wood JPM, Plunkett M, Previn V, et al.
Nanosecond‐laser application in intermediate AMD: 12‐month results of fundus appearance and macular function.
English
2019

Purpose:
A novel, ultra-low energy nanosecond laser (retinal rejuvenation therapy) has been developed with the aim to slow progression of early age-related macular degeneration (AMD). The safety, changes in fundus characteristics and macular function in a cohort of participants with bilateral intermediate AMD are reported.

Methods:
DESIGN: Prospective non-randomised, pilot intervention study.
PARTICIPANTS OR SAMPLES: Subjects with bilateral intermediate AMD (n = 50, aged 50-75 years).
METHODS: Ultra-low energy laser pulses applied in 12 spots around the macula of one eye (0.15-0.45 mJ), using 400 μm diameter spot, 3 nanosecond pulse length, 532 nm wavelength and energy titrated to each patient.

MAIN OUTCOME MEASURES:
Best corrected visual acuity, drusen area and macular sensitivity (flicker perimetry) at baseline and at 3, 6 and 12 months post-laser.

Results:
Treatment was painless with no clinically visible lesions. No participant developed choroidal neovascularization, while two with thin central retinal thickness at baseline developed atrophy at 12-month follow up. Drusen area was reduced in 44% of treated eyes and 22% of untreated fellow eyes, with changes in drusen and function not being coincident. Improvement in flicker threshold within the central 3° was observed in both the treated and untreated fellow eyes at 3 months post-laser. Of the 11 eyes at greatest risk of progression (flicker defect >15 dB), seven improved sufficiently to be taken out of this high-risk category.

Conclusion:
A single unilateral application of nanosecond laser to the macula produced bilateral improvements in macula appearance and function. The nanosecond retinal rejuvenation therapy laser warrants ongoing evaluation as an early intervention for AMD.

Details Guymer RH, Brassington KH, Dimitrov P, et al. Nanosecond‐laser application in intermediate AMD: 12‐month results of fundus appearance and macular function. Clin Exp Ophthalmol. 2014.42(5):466–479. DOI: 10.1111/ceo.12247.
Source Clin Exp Ophthalmol.
Author(s) Guymer RH, Brassington KH, Dimitrov P, et al.
Splitting the Lumps: The Importance of Phenotyping Drusen.
English
2019

Details Guymer RH Splitting the Lumps: The Importance of Phenotyping Drusen. Ophthalmology. 2018.125(1):6-7. DOI: 10.1016/j.ophtha.2017.09.007.
Source Ophthalmology.
Author(s) Guymer RH
Clinical Classification of Age-related Macular Degeneration.
English
2019

Purpose:
To develop a clinical classification system for age-related macular degeneration (AMD).
DESIGN: Evidence-based investigation, using a modified Delphi process.
PARTICIPANTS: Twenty-six AMD experts, 1 neuro-ophthalmologist, 2 committee chairmen, and 1 methodologist.

Methods:
Each committee member completed an online assessment of statements summarizing current AMD classification criteria, indicating agreement or disagreement with each statement on a 9-step scale. The group met, reviewed the survey results, discussed the important components of a clinical classification system, and defined new data analyses needed to refine a classification system. After the meeting, additional data analyses from large studies were provided to the committee to provide risk estimates related to the presence of various AMD lesions. MAIN OUTCOME MEASURES: Delphi review of the 9-item set of statements resulting from the meeting.

Results:
Consensus was achieved in generating a basic clinical classification system based on fundus lesions assessed within 2 disc diameters of the fovea in persons older than 55 years. The committee agreed that a single term, age-related macular degeneration, should be used for the disease. Persons with no visible drusen or pigmentary abnormalities should be considered to have no signs of AMD. Persons with small drusen (<63 μm), also termed drupelets, should be considered to have normal aging changes with no clinically relevant increased risk of late AMD developing. Persons with medium drusen (≥ 63-<125 μm), but without pigmentary abnormalities thought to be related to AMD, should be considered to have early AMD. Persons with large drusen or with pigmentary abnormalities associated with at least medium drusen should be considered to have intermediate AMD. Persons with lesions associated with neovascular AMD or geographic atrophy should be considered to have late AMD. Five-year risks of progressing to late AMD are estimated to increase approximately 100 fold, ranging from a 0.5% 5-year risk for normal aging changes to a 50% risk for the highest intermediate AMD risk group.

Conclusion:
The proposed basic clinical classification scale seems to be of value in predicting the risk of late AMD. Incorporating consistent nomenclature into the practice patterns of all eye care providers may improve communication and patient care.

Details Ferris FL, Wilkinson CP, Bird A, et al. Clinical Classification of Age-related Macular Degeneration. Ophthalmology. 2013.120:844–851. DOI: 10.1016/j.ophtha.2012.10.036.
Source Ophthalmology.
Author(s) Ferris FL, Wilkinson CP, Bird A, et al.
Sub-Threshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial.
English
2019

Purpose:
There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Sub-threshold nanosecond laser (SNL) treatment has been shown in preclinical studies and a pilot study in intermediate AMD (iAMD) to reverse the signs of AMD without causing damage to the overlying retina, thus demonstrating promise as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD.

Methods:

The Laser intervention in Early stages of Age-related macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial conducted from 2012-2015.
Participants: 292 participants with bilateral large drusen and without optical coherence tomography signs of atrophy.
Interventions: Participants were randomly assigned to receive SNL or sham treatment to the study eye at six-monthly intervals.

Results:

The primary efficacy outcome was the time to develop late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. Overall, the progression to late AMD was not significantly slowed with SNL compared to sham treatment (adjusted hazard ratio [HR] 0.61, 95% CI 0.33-1.14; p=0.122). However, a post-hoc analysis showed that progression was slowed for the 222 (76.0%) paricipants without coexistent reticular pseudodrusen (RPD) at baseline (adjusted HR 0.23, 95% CI 0.09–0.59; p=0.002), whilst an increased progression rate (adjusted HR 2.56, 95% CI 0.80–8.18; p=0.112) was observed for the 70 (24.0%) participants with RPD with SNL treatment (adjusted interaction p=0.002). Differences between the groups in serious adverse events were not significant.

Conclusion:

In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT laser, but they should not be extrapolated to other short pulse lasers.

Details Guymer RH, Wu Z, Hodgson LAB, et al. Sub-Threshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial. Ophthalmology. 2018. DOI: 10.1016/j.ophtha.2018.09.015.
Source Ophthalmology.
Author(s) Ophthalmology.
Retinal Damage Profiles and Neuronal Effects of Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel 3-Nanosecond Pulse Laser.
English
2019

Purpose:
To determine detailed effects to retinal cells and, in particular, neurons following laser photocoagulation using a conventional 532 nm Nd:YAG continuous wave (CW) laser. Furthermore, to determine whether a novel 3 ns pulse laser (retinal regeneration therapy; 2RT) could specifically ablate retinal pigment epithelium (RPE) cells without causing collateral damage to other retinal cells.

Methods:
Adult Dark Agouti (DA) rats were separated into four groups: control, CW laser (12.7 J/cm 2 /pulse, 100 ms pulse duration), or 3 ns pulse 2RT laser at one of two energy settings (‘‘High,’’ 2RT-H, 163 mJ/cm 2 /pulse; ‘‘Low,’’ 2RT-L, 109 mJ/cm 2 /pulse). Animals were treated and killed after 6 hours to 7 days, and retina/RPE was analyzed by histologic assessment, Western blot, polymerase chain reaction, and immunohistochemistry.

Results:
Both lasers caused focal loss of RPE cells with no destruction of Bruch’s membrane; RPE cells were present at lesion sites again within 7 days of treatments. CW and 2RT-H treatments caused extensive and moderate damage, respectively, to the outer retina. There were no obvious effects to horizontal, amacrine, or ganglion cells, as defined by immunolabeling, but an activation of PKCa within bipolar cells was noted. There was little discernible damage to any cells other than the RPE with the 2RT-L treatment.

Conclusion:
Conventional laser photocoagulation caused death of RPE cells with associated widespread damage to the outer retina but little influence on the inner retina. The novel 3 ns 2RT laser, however, was able to selectively kill RPE cells without causing collateral damage to photoreceptors. Potential benefits of this laser for clinical treatment of diabetic macular edema are discussed.

Details Wood JPM, Shibeeb OS, Plunkett M, et al. Retinal Damage Profiles and Neuronal Effects of Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel 3-Nanosecond Pulse Laser. IOVS. 2013.54(3):2305–2318. DOI: 10.1167/iovs.12-11203.
Source IOVS.
Author(s) Wood JPM, Shibeeb OS, Plunkett M, et al.
Nanosecond laser treatment for age-related macular degeneration does not induce focal vision loss or new vessel growth in the retina.
English
2019

Purpose:
Subthreshold, nanosecond pulsed laser treatment shows promise as a treatment for age-related macular degeneration (AMD); however, the safety profile needs to be robustly examined. The aim of this study was to investigate the effects of laser treatment in humans and mice.

Methods:
Patients with AMD were treated with nanosecond pulsed laser at subthreshold (no visible retinal effect) energy doses (0.15–0.45 mJ) and retinal sensitivity was assessed with microperimetry. Adult C57BL6J mice were treated at subthreshold (0.065 mJ) and suprathreshold (photoreceptor loss, 0.5 mJ) energy settings. The retinal and vascular responses were analyzed by fundus imaging, histologic assessment, and quantitative PCR.

Results:
Microperimetry analysis showed laser treatment had no effect on retinal sensitivity under treated areas in patients 6 months to 7 years after treatment. In mice, subthreshold laser treatment induced RPE loss at 5 hours, and by 7 days the RPE had retiled. Fundus imaging showed reduced RPE pigmentation but no change in retinal thickness up to 3 months. Electron microscopy revealed changes in melanosomes in the RPE, but Bruch’s membrane was intact across the laser regions. Histologic analysis showed normal vasculature and no neovascularization. Suprathreshold laser treatment did not induce changes in angiogenic genes associated with neovascularization. Instead pigment epithelium–derived factor, an antiangiogenic factor, was upregulated.

Conclusion: 
In humans, low-energy, nanosecond pulsed laser treatment is not damaging to local retinal sensitivity. In mice, treatment does not damage Bruch’s membrane or induce neovascularization, highlighting a reduced side effect profile of this nanosecond laser when used in a subthreshold manner.

Details Vessey KA, Ho T, Jobling AI, et al. Nanosecond laser treatment for age-related macular degeneration does not induce focal vision loss or new vessel growth in the retina. Invest Ophthalmol Vis Sci. 2018.59:731–745. DOI: 10.1167/iovs.17-23098.
Source Invest Ophthalmol Vis Sci.
Author(s) Vessey KA, Ho T, Jobling AI, et al.
Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser.
English
2019

Purpose:
Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). The thermal nature of this procedure, however, defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, non-thermal laser (Retinal Regeneration Therapy; 2RT) at clinically relevant energy levels.

Methods:
Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532nm, 100ms pulse duration) or a short-pulse (2RT; 532nm, Q-switched, 3ns pulse) laser. Settings were at visible threshold for the CW laser (12.7J/cm 2 /pulse) and at supra- and sub-visible threshold for the 2RT laser (“High”, 2RT-H, 163mJ/cm 2 /pulse; “Low”, 2RT-L, 109mJ/cm 2 /pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR and Western blotting.

Results:

The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Müller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the sub-threshold setting. 

Conclusion:
The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.

Details Chidlow G, Shibeeb OS, Plunkett M, et al. Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser. IOVS. 2013.54(3):2319–2332. DOI: 10.1167/iovs.12-11204.
Source IOVS.
Author(s) IOVS.
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