Subthreshold Photocoagulation Using Endpoint Management in the PASCAL® System for Diffuse Diabetic Macular Edema

We evaluated subthreshold photocoagulation using endpoint management (EPM) for the treatment of diabetic macular edema (DME). The study enrolled 10 eyes from 10 patients (6 men and 4 women) with DME. The entry criteria included central macular thickness (CMT) ≥ 300 μm and decimal visual acuity (VA) ≤ 0.5. The primary endpoints were VA (logMAR) and CMT at 6 months follow-up. Secondary endpoints included fundus autofluorescence, macular volume (MV), and macular sensitivity (MS). We used the PASCAL Streamline Yellow® (wavelength, 577 nm) system to perform grid pattern laser photocoagulation at 50% of the threshold (size, 100 μm; duration, 0.015 s; spacing, 0.5; and energy, 4.5–7.8 mJ). At 6 months posttreatment, CMT was significantly decreased, while there were no significant changes in macular sensitivity, mean BCVA (logMAR), or macular volume. Autofluorescence imaging revealed no changes after treatment in 6 of 10 eyes. No eyes exhibited subjective symptoms of scotoma after photocoagulation. Optical coherence tomography showed the complete resolution of macular edema in 4 eyes (40%) after a single treatment; MS was increased in all 4 of these eyes at 6 months posttreatment. In conclusion, subthreshold photocoagulation using EPM is safe and effective for DME treatment and preserves MS. This trial is registered with UMIN000012401

Sublethal Photothermal Stimulation with a Micropulse Laser Induces Heat Shock Protein Expression in ARPE-19 Cells

Purpose/Aim of the Study. Subthreshold micropulse diode laser photocoagulation is an effective treatment for macular edema. The molecular mechanisms underlying treatment success are poorly understood. Therefore, we investigated the effects of sublethal laser energy doses on a single layer of densely cultured ARPE-19 cells as a model of the human retinal pigment epithelium (RPE). Materials and Methods. A single layer of densely cultured human ARPE-19 cells was perpendicularly irradiated with a micropulse diode laser. Nonirradiated cells served as controls. Sublethal laser energy was applied to form a photocoagulation-like area in the cultured cell layers. Hsp70 expression was evaluated using quantitative polymerase chain reaction and immunocytochemistry. Results. Photocoagulation-like areas were successfully created in cultured ARPE-19 cell layers using sublethal laser energy with our laser irradiation system. Hsp70 mRNA expression in cell layers was induced within 30 min of laser irradiation, peaking at 3 h after irradiation. This increase was dependent on the number of laser pulses. Hsp70 upregulation was not observed in untreated cell layers. Immunostaining indicated that Hsp70 expression occurred concentrically around laser irradiation sites and persisted for 24 h following irradiation. Conclusion. Sublethal photothermal stimulation with a micropulse laser may facilitate Hsp70 expression in the RPE without inducing cellular damage

Real-world management of treatment-naïve diabetic macular oedema : 2-year visual outcome focusing on the starting year of intervention from STREAT-DMO study

Background/aims To investigate the yearly change of real-world outcomes for best corrected visual acuity (BCVA) after 2-year clinical intervention for treatment-naïve diabetic macular oedema (DMO). Methods Retrospective analysis of aggregated, longitudinal medical records obtained from 27 retina specialised institutions in Japan from Survey of Treatment for DMO database. A total of 2049 treatment-naïve centre involving DMO eyes of which the initial intervention started between 2010 and 2015, and had been followed for 2 years, were eligible. As interventions, antivascular endothelial growth factor (VEGF) agents, local corticosteroids, macular photocoagulation and vitrectomy were defined. In each eye, baseline and final BCVA, the number of each intervention for 2 years was extracted. Each eye was classified by starting year of interventional treatment. Results Although baseline BCVA did not change by year, 2-year improvement of BCVA had been increased, and reached to +6.5 letters in the latest term. There is little difference among starting year about proportions of eyes which BCVA gained >15 letters, in contrast to those which lost >15 letters were decreased by year. The proportion of eyes receiving anti-VEGF therapy was dramatically increased, while those receiving the other therapies were gradually decreased. The proportion of eyes which maintained socially good vision of BCVA>20/40 has been increased and reached to 59.0% in the latest term. Conclusion For recent years, treatment patterns for DMO have been gradually but certainly changed; as a result, better visual gain, suppression of worsened eyes and better final BCVA have been obtained. Anti-VEGF therapy has become the first-line therapy and its injection frequency has been increasing

Impact of Treating Age-Related Macular Degeneration before Visual Function Is Impaired

Visual outcomes of age-related macular degeneration (AMD) have substantially improved via anti-vascular endothelial growth factor (anti-VEGF) therapy. However, the treatment effects vary among individuals. Medical charts of 104 eyes (104 patients) with AMD, treated with anti-VEGF drugs and followed up for 12–36 months, were retrospectively analyzed. Logistic regression analyses adjusted for age showed that eyes with an initial best-corrected visual acuity (BCVA) < 0.3 in the logarithm of the minimum angle of resolution (logMAR) were a positive predictor (odds ratio = 3.172; 95% confidence interval [CI] = 1.029–9.783; p = 0.045), and the presence of initial fibrovascular pigment epithelial detachment (PED) was a negative predictor (0.222; 0.078–0.637; p = 0.005) of maintained or improved BCVA at the final visit. Kaplan–Meier survival analysis showed that eyes with an initial BCVA < 0.3 (Cox hazard ratio = 2.947; 95% CI = 1.047–8.289; p = 0.041) had a better survival rate after adjusting for age when failure was defined as a BCVA reduction ≥ 0.2 of logMAR. Eyes with an initial BCVA < 0.3 belonged to younger patients; more frequently had subretinal fluid as an exudative change; and less frequently had intraretinal fluid, submacular hemorrhage, and fibrovascular PED. Initiating anti-VEGF treatment before BCVA declines and advanced lesions develop would afford better visual outcomes for AMD eyes in the real-world clinic, although further analyses are required

Subthreshold Micropulse Photocoagulation for Persistent Macular Edema Secondary to Branch Retinal Vein Occlusion including Best-Corrected Visual Acuity Greater Than 20/40

To assess the efficacy of subthreshold micropulse diode laser photocoagulation (SMDLP) for persistent macular edema secondary to branch retinal vein occlusion (BRVO), including best-corrected visual acuity (BCVA) > 20/40, thirty-two patients (32 eyes) with macular edema secondary to BRVO were treated by SMDLP. After disease onset, all patients had been followed for at least 6 months prior to treatment. Baseline Snellen visual acuity was used to categorize the eyes as BCVA ≤ 20/40 (Group I) or BCVA > 20/40 (Group II). Main outcome measures were reduction in central macular thickness (CMT) in optical coherence tomography (OCT) and BCVA at 6 months. In the total subject-pool at 6 months, BCVA had not changed significantly but CMT was significantly reduced. Group I exhibited no significant change in CMT at 3 months but exhibited significant reductions at 6 and 12 months. Group II exhibited a marginally significant reduction in CMT at 3 months and a significant reduction at 6 months. In patients with persistent macular edema secondary to BRVO, SMDLP appears to control macular edema with minimal retinal damage. Our findings suggest that SMDLP is an effective treatment method for macular edema in BRVO patients with BCVA > 20/40

Temperature Increase and Damage Extent at Retinal Pigment Epithelium Compared between Continuous Wave and Micropulse Laser Application

Continuous wave (CW) and microsecond pulse (MP) laser irradiations were compared regarding cell damage and laser-induced temperature rise at retinal pigment epithelium (RPE). The RPE of porcine RPE-choroid-sclera explants was irradiated with a 577 nm laser in CW or MP mode (5% or 15% duty cycle (DC)) for 20 ms or 200 ms at an average laser power of 20–90 mW. Cell viability was investigated with calcein-AM staining. Optoacoustic (OA) technique was employed for temperature measurement during irradiation. For 200 ms irradiation, the dead cell area (DCA) increased linearly (≈1600 µm2/mW) up to the average power of 40 mW for all modes without significant difference. From 50 mW, the increase of DCA of MP-5% significantly dropped to 610 µm2/mW (p < 0.05), likely due to the detected microbubble formation. OA temperature measurement showed a monotonic temperature increase in CW mode and a stepwise increase in MP mode, but no significant difference in the average temperature increase at the same average power, consistent with the temperature modeling. In conclusion, there is no difference in the average temperature rise between CW and MP modes at the same average power regardless of DC. At lower DC, however, more caution is required regarding mechanical damage due to microbubble formation