LASER RESENSITIZATION OF MEDICALLY UNRESPONSIVE NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Efficacy and Implications.

PURPOSE: Drug tolerance is the most common cause of treatment failure in neovascular age-related macular degeneration. "Low-intensity/high-density" subthreshold diode micropulse laser (SDM) has been reported effective for a number of retinal disorders without adverse effects. It has been proposed that SDM normalizes retinal pigment epithelial function. On this basis, it has been postulated that SDM treatment might restore responsiveness to anti-vascular endothelial growth factor drugs in drug-tolerant eyes. METHODS: Subthreshold diode micropulse laser treatment was performed in consecutive eyes unresponsive to all anti-vascular endothelial growth factor drugs, including at least three consecutive ineffective aflibercept injections. Monthly aflibercept was resumed 1 month after SDM treatment. RESULTS: Thirteen eyes of 12 patients, aged 73 to 97 years (average, 84 years), receiving 16 to 67 (average, 34) anti-vascular endothelial growth factor injections before SDM treatment were included and followed for 3 months to 7 months (average, 5 months) after SDM treatment. After SDM treatment and resumption of aflibercept, 92% (12 of 13) of eyes improved, with complete resolution of macular exudation in 69% (9 of 13). Visual acuity remained unchanged. Central and maximum macular thicknesses significantly improved. CONCLUSION: Subthreshold diode micropulse laser treatment restored drug response in drug-tolerant eyes with neovascular age-related macular degeneration. Based on these findings, a theory of SDM action is proposed, suggesting a wider role for SDM as retinal reparative/protective therapy.

No-Dose Photodynamic Therapy Against Half-Dose Photodynamic Therapy for Treatment of Central Serous Chorioretinopathy.

INTRODUCTION: This study aimed to describe the effects of no-dose full-fluence photodynamic therapy without verteporfin (no-dose PDT) and to compare no-dose PDT with half-dose verteporfin full-fluence photodynamic therapy (HDFF PDT) for managing chronic central serous chorioretinopathy (cCSC). METHODS: This retrospective study evaluated 11 patients with chronic recurrent CSC treated with no-dose PDT between January 2019 and March 2022. Most of these patients were also treated with HDFF PDT a minimum of 3 months before and were considered as the control group. We described the changes of best corrected visual acuity (BCVA), maximum subretinal fluid (mSRF), foveal subretinal fluid (fSRF), and choroidal thickness (CT) 8 ± 2 weeks after no-dose PDT, and we compared BVCA, mSRF, fSRF, and CT of no-dose PDT with those of the of same patients previously treated with HDFF PDT. RESULTS: Fifteen eyes of 11 patients (10 male, mean age 54 ± 12 years) received no-dose PDT; among these, 10 eyes of 8 patients (7 male, mean age 53 ± 12 years) also received HDFF PDT. Three eyes showed complete resolution of fSRF after no-dose PDT. No significant differences were disclosed between treatment with and without verteporfin comparing BCVA, mSRF, fSRF, and CT at baseline and 8 ± 2 weeks from the treatment (p > 0.05 in all analyses). CONCLUSION: BVCA and CT significantly improved after no-dose PDT. Short-term functional and anatomical treatment outcomes for cCSC were similar for HDFF PDT and no-dose PDT. We hypothesize that the potential benefits of no-dose PDT may arise from thermal elevation that triggers and enhances photochemical activities by endogenous fluorophores, activating a biochemical cascade response that rescues/replaces sick, dysfunctional retinal pigment epithelial (RPE) cells. Results of this study suggest the potential value of a prospective clinical trial to evaluate no-dose PDT for managing cCSC, especially when verteporfin is contraindicated or unavailable.

Laser-induced changes in intraretinal oxygen distribution in pigmented rabbits.

PURPOSE: To make the first measurements of intraretinal oxygen distribution and consumption after laser photocoagulation of the retina and to compare the efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in achieving an oxygen benefit in the treated area. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth before and after laser treatment in anesthetized, mechanically ventilated, Dutch Belted rabbits (n = 11). Laser lesions were created by using a range of power levels from an 810-nm diode laser coupled with an operating microscope delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW delivery in each eye. RESULTS: Sufficient power levels of both the CW and MP laser reduced outer retinal oxygen consumption and increased oxygen level within the retina. At these power levels, which correlated with funduscopically visible lesions, there was histologically visible damage to the RPE and photoreceptors. Retinal damage was energy dependent but short-duty-cycle MP delivery was more selective in terms of retinal cell damage, with a wider safety range in comparison with CW delivery. CONCLUSIONS: The relationship between laser power level and mode of delivery and the resultant changes in oxygen metabolism and oxygen level in the retina was determined. Only partial destruction of RPE and photoreceptors is necessary, to produce a measurable oxygen benefit in the treated area of retina.

Monitoring retinal function during transpupillary thermotherapy for occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To use focal electroretinography to evaluate changes in retinal function during transpupillary thermotherapy (TTT) for neovascular age-related macular degeneration (ARMD). METHODS: Sixteen eyes of 16 patients with ARMD with occult choroidal neovascularization (CNV) were studied. A 630-nm photocoagulator aiming beam was modified for use as a 41-Hz square-wave focal electroretinogram (fERG) stimulus. The stimulus was presented on a light-adapting background by a Goldmann-type lens (visual angle, 18 degrees; mean luminance, 50 cd/m(2)). fERGs were continuously monitored before, during, and after TTT for occult CNV. The amplitude and phase of the fERG's fundamental harmonic were measured. RESULTS: No suprathreshold or adverse clinical events occurred during the course of the study. fERG amplitude decreased transiently during TTT (23% +/- 9% [SE]; P < 0.05). The decrease in amplitude was greatest 16 to 20 seconds and 32 to 40 seconds after the onset of TTT. It was followed by a recovery to baseline amplitude during TTT (48 to 60 seconds after TTT was begun). Within 60 seconds after TTT was completed, fERG amplitude was within the range of baseline. TTT did not alter the fERG phase. Mean fERG amplitudes and phases recorded 1 week and 1 month after TTT were comparable to mean pretreatment levels. CONCLUSIONS: fERG amplitude decreases transiently during TTT, despite the absence of ophthalmoscopically apparent lesions. Intraoperative amplitude depression may result from an adaptation effect to laser light energy and/or hyperthermia, resulting in desensitization of cone photoreceptors and bipolar cells. Treatment sites are electrophysiologically functional 1 month after TTT. Detailed parametric study of a larger patient group is needed to determine whether fERG testing is potentially useful for monitoring and perhaps for controlling and optimizing TTT for choroidal neovascularization.

Subthreshold and micropulse diode laser photocoagulation.

Retinal laser photocoagulation is a proven, effective treatment for various retinal disorders. Common clinical protocols use intra-operatively visible endpoints that cause iatrogenic chorioretinal damage. For this reason, laser therapy is normally limited to levels of disease severity for which the benefit-to-risk ratio justifies its application. The use of 810 nm diode lasers in the MicroPulse mode offers the surgeon the possibility to minimize iatrogenic retinal damage. A less destructive laser therapy with a more favorable benefit-to-risk ratio could justify treatment earlier in the course of the disease, allowing for stabilization or improvement of less compromised visual functions.

Evolution of retinal laser therapy: minimum intensity photocoagulation (MIP). Can the laser heal the retina without harming it?

Laser photocoagulation is a photo-thermal therapy validated by landmark studies and commonly accepted as the standard of care for various retinal diseases. Although its mechanism of action is still not completely understood, it is normally administered with visible endpoints, true intra-retinal burns that cause chorioretinal scars, which, with time, evolve into expanding areas of atrophy. New hypotheses on the mechanism of action of laser photocoagulation suggest that its therapeutic benefits derive from biologic activities that cannot be inducted within the "burned" area of photocoagulation necrosis, but that occur in the adjacent surrounding areas affected by a lower, sub-lethal, photo-thermal elevation. Thus, the iatrogenic chorioretinal damage caused by visible endpoint photocoagulation may be redundant and an equally effective laser therapy could be administered with minimum intensity photocoagulation (MIP) using laser protocols aiming to create only non-lethal photo-thermal elevations with no intraoperative visible endpoint. It is the purpose of this paper to review laser techniques and clinical protocols that have been utilized to administer retina-sparing MIP treatments that hold the promise of healing the retina while minimizing the iatrogenic harm.

Subthreshold diode micropulse laser photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema: a review.

PURPOSE: To present the state-of-the-art of subthreshold diode laser micropulse photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema (DME). METHOD: To review the role and evolution of retinal laser treatment for DME. RESULTS: Thermal laser retinal photocoagulation has been the cornerstone of treatment for diabetic macular edema for over four decades. Throughout, laser induced retinal damage produced by conventional photocoagulation has been universally accepted as necessary to produce a therapeutic benefit, despite the inherent risks, adverse effects and limitations of thermally destructive treatment. Recently, SDM, performed as invisible retinal phototherapy for DME, has been found to be effective in the absence of any retinal damage or adverse effect, fundamentally altering our understanding of laser treatment for retinal disease. SUMMARY: The discovery of clinically effective and harmless SDM treatment for DME offers exciting new information that will improve our understanding of laser treatment for retinal disease, expand treatment indications, and improve patient outcomes.

Subthreshold diode laser micropulse photocoagulation for the treatment of diabetic macular edema.

Diabetic macular edema (DME) is a sight-threatening complication of diabetic retinopathy, the leading cause of visual loss in the working-age population in the industrialized and emerging world. The standard of care for DME is focal/grid laser photocoagulation, which is proven effective in reducing the risk of vision loss, but inherently destructive and associated with tissue damage and collateral effects. Subthreshold diode laser micropulse photocoagulation is a nondestructive tissue-sparing laser procedure, which, in randomized controlled trials for the treatment of DME, has been found equally effective as conventional photocoagulation. Functional and anatomical outcomes from four independent randomized controlled trials provide level one evidence that vision stabilization/improvement and edema resolution/reduction can be elicited with less or no retinal damage, and with fewer or no complications. This review describes the principles of subthreshold diode laser micropulse photocoagulation, its treatment modalities and clinical outcomes in the context of standard laser treatments and of emerging nonlaser therapies for DME.

Micropulsed diode laser therapy: evolution and clinical applications.

Many clinical trials have demonstrated the clinical efficacy of laser photocoagulation in the treatment of retinal vascular diseases, including diabetic retinopathy. There is, however, collateral iatrogenic retinal damage and functional loss after conventional laser treatment. Such side effects may occur even when the treatment is appropriately performed because of morphological damage caused by the visible endpoint, typically a whitening burn. The development of the diode laser with micropulsed emission has allowed subthreshold therapy without a visible burn endpoint. This greatly reduces the risk of structural and functional retinal damage, while retaining the therapeutic efficacy of conventional laser treatment. Studies using subthreshold micropulse laser protocols have reported successful outcomes for diabetic macular edema, central serous chorioretinopathy, macular edema secondary to retinal vein occlusion, and primary open angle glaucoma. The report includes the rationale and basic principles underlying micropulse diode laser therapy, together with a review of its current clinical applications.