Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration

doi:10.1016/S0002-9394(02)01691-4

American Journal of Ophthalmology

Volume 134, Issue 4, October 2002, Pages 577-585

https://doi.org/10.1016/S0002-9394(02)01691-4 Get rights and content

Abstract

PURPOSE: To determine the predictors of drusen reduction in eyes with nonexudative age-related macular degeneration (ARMD) treated with subthreshold infrared (810 nm) diode laser macular grid photocoagulation. Additionally, to determine the relationship of laser-induced drusen reduction and best-corrected visual acuity (BCVA) 18 months after laser treatment.

DESIGN: Randomized controlled clinical trial.

METHODS: Fifty patients (100 eyes) with bilateral nonexudative ARMD were enrolled at two centers. One eye of each patient was randomized to the observation; the other eye was treated with 48 subthreshold (invisible end point) applications of infrared (810 nm) diode laser in a macular grid pattern. The eyes that received subthreshold laser treatment were compared with the eyes that received no treatment. The baseline fundus characteristics (number, size, and distribution of drusen, as well as focal hyperpigmentation) from two macula areas (central 1500 μ diameter, pericentral 1500 μ ring area) on stereo color photographs, the number of laser-induced lesions, and the area of laser induced retinal pigment epithelial (RPE) lesions on fluorescein angiography 3 months after treatment were studied as predictors of major drusen reduction (≥ 50% drusen reduction from baseline) 18 months after laser treatment. BCVA at baseline and 18 months later was compared in observation eyes and in laser-treated eyes.

RESULTS: Eighteen months after randomization, 24 (48%) of 50 eyes treated with subthreshold laser had major drusen reduction compared with three (6%) of 50 observation eyes (P = .00001). At 3 months post-treatment in laser-treated eyes with major drusen reduction, the mean number of laser-induced lesions on fluorescein angiography was 30.7 and the mean area of RPE change was 0.81 mm² compared with 14.8 laser-induced lesions and 0.35 mm² area of RPE change in eyes without major drusen reduction (P = .0001 and P = .0003, respectively). At baseline, fundus characteristics were not significantly different between observation eyes and laser-treated eyes or between the major drusen reduction group and the nonmajor drusen reduction group. At 18 months after treatment, BCVA was not significantly different in laser-treated eyes and in observation eyes.

CONCLUSIONS: Subthreshold infrared (810 nm) diode laser macular grid photocoagulation in eyes with nonexudative ARMD significantly reduced drusen 18 months after laser treatment. Both the number of subthreshold laser lesions and the area of RPE changes visible on fluorescein angiography 3 months after treatment appeared to be predictors for major drusen reduction 18 months after treatment. However, it remains to be determined whether laser-induced drusen reduction is beneficial for visual acuity or reduces the incidence of choroidal neovascularization (CNV) in eyes with nonexudative ARMD.

Section snippets

Design

Data were analyzed from a multicenter, prospective, randomized, and controlled clinical trial.

Methods

All fifty patients (100 eyes) with bilateral nonexudative ARMD who were enrolled into a randomized controlled clinical trial at two of the centers (Shiley Eye Center, UCSD, San Diego, California; University of Pittsburgh, Pittsburgh, Pennsylvania) were analyzed as a substudy of the prospective randomized controlled clinical trial (PTAMD study, bilateral study arm).

The PTAMD study’s specific patient selection, randomization, laser treatment, and patient follow-up methodologies have been reported

Results

A total of 100 eyes of 50 patients were enrolled in this study (32 patients were female and 18 patients were male). The mean age was 76.68 years, ranging from 50 to 95.5 years. At 18 months post-randomization, major drusen reduction was seen in 48% (24 of 50) of laser-treated eyes and in 6% (3 of 50) of observation eyes. The percentage of eyes showing major drusen reduction was significantly greater in laser-treated eyes compared with observation eyes (P = .00001, Fisher exact test).

The

Discussion

A variety of prophylactic laser treatments for patients with high-risk drusen has been evaluated.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 Green laser has been used in most studies10, 11, 12, 14, 16, 17, 19, 22, 23, 24, 25, 26 with different visible end points from barely visible to grayish-white. The different laser spot sizes, numbers, and patterns have been used with attempts to treat directly over drusen10, 13, 16, 17, 20, 21, 22, 23 or indirectly by

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Citation Excerpt :
For those subjects in the PTAMD study, only the eyes that had not been randomized to subthreshold laser treatment were used, because laser treatment could conceivably alter the likelihood of an eye converting from dry to wet AMD. Furthermore, it is well known that laser application to eyes with drusen promotes drusen resorption, modifying the typical natural history of drusen morphology.10–12 Our subjects were seen at baseline and subsequently at planned annual visits for up to 8 years in AREDS and for more than 5 years in the PTAMD study.
To use longitudinal quantitative morphologic and visual acuity (VA) data to investigate the risk of choroidal neovascularization (CNV) event occurrence in eyes with dry age-related macular degeneration (AMD).
Prospective observational study.
A total of 513 participants (844 eyes) followed longitudinally in one center enrolled in the Age-Related Eye Disease Study (AREDS) or the Prophylactic Treatment of AMD Study (PTAMD).
We assessed images of previously obtained fundus photographs for the presence of macular pigmentation, drusen area, and drusen distribution (number and size), and fellow eye CNV status at baseline. Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity at each visit and the age of each subject were obtained. We used a longitudinal logistic mixed-effects model with random intercepts fitted to event occurrences to assess risk on a per eye basis.
Odds ratios for CNV event.
Thirty-one subjects (6.0%) had events. Only VA changes over time and follow-up interval showed statistically significant effects. Several statistical models that included VA at the previous visit were used. In 2 models, 3 categories of VA were used: ≤75 letters, >75 and ≤85 letters, and >85 letters. Two categories were used for follow-up: ≤3 years versus >3 years or ≤1 year versus >1 year. In the first model with categorization at 3 years, a decrease in acuity from the >85 letter category to ≤75 letters increased the odds of CNV by 16.9 times (P = 0.022). In the model with categorization at 1 year, a decrease in acuity from the >85-letter category to ≤75 letters increased the odds of CNV by 21.4 times (P = 0.0175). Differences between the follow-up intervals were significant (P = 0.043) and indicated a more than 7-fold increase in the odds. Changes in morphologic features of the macula did not show significant effects.
A decrease in VA to ≤75 ETDRS letters in an eye with an initial ETDRS baseline acuity of >85 letters increases the likelihood of CNV by approximately 20-fold. This likelihood also increases with aging.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Vectorial release of matrix metalloproteinases (MMPs) from porcine RPE-choroid explants following selective retina therapy (SRT): Towards slowing the macular ageing process
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However, both conventional continuous wave lasers (Roider et al., 1993a) and low energy diode lasers (Mojana et al., 2011), although targeting RPE, also cause irreversible collateral thermal damage to the outer retina. Therefore, in the clinical trials, laser treatment was applied only once, the number of laser spots was kept to a minimum and spots were delivered into the peripheral macula to avoid undue damage of the central macula (Ho et al., 1999; Rodanant et al., 2002; Owens et al., 2006; Maguire et al., 2006). Hence, improvement of visual function may be expected to be limited (Ho et al., 1999; Friberg et al., 2009) or absent (Owens et al., 2006).
The purpose of this study was to investigate release of matrix metalloproteinases (MMP) 2 and 9 during retinal pigment epithelium (RPE) wound healing after Selective Retina Therapy (SRT) with laser energy levels below and above the threshold of RPE cell death. Following exposure to SRT using a prototype pulsed Nd:YLF laser with energies of 80–180 mJ/cm² fresh porcine RPE-monolayers with Bruch's membrane and choroid were cultured in modified Ussing chambers which separate the apical (RPE-facing) and basal (choroid facing) sides of the RPE monolayer. Threshold energy for RPE cell death and wound healing were determined with calcein-AM viability test. Inactive and active forms of MMP 2 and 9 were quantified within tissue samples and in the culture medium of the apical and basal compartments of the Ussing chamber using gelatine zymography. Laser energies of 160–180 mJ/cm² resulted in cell death within 1 h while 120–140 mJ/cm² resulted in delayed death of exposed RPE cells. All cells survived 80 and 100 mJ/cm². Laser spots healed within 6 days after SRT accompanied by a transient vectorial increase of MMPs. SRT with 180 mJ/cm² increased active MMP 2 by 1.9 (p < 0.05) and 1.6 (p < 0.05) fold in tissue and basal compartments, respectively, without alterations in the apical compartment. Pro-MMP 2 levels were also significantly increased in all compartments (p < 0.05). Release of MMP 9 was not altered. Laser energy below the threshold of RPE cell death did not alter the release of MMP 2 or 9. The findings suggest that the release of active MMP 2 on the basal side of the RPE during wound healing following SRT may address age-related pathological changes of Bruch's membrane with a potential to slow degenerative macular ageing processes before irreversible functional loss has occurred.
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Statement and supplementary statement from the BVA, the DOG, and the RG on laser treatment of drusen in age-related macular degeneration (AMD): August 2017, update October 2018
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^☆: This work was supported by the National Eye Institute Grant EYO7366 and Research to Prevent Blindness, Inc.

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Original articlePredictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration☆

Abstract

Section snippets

Design

Methods

Results

Discussion

Ophthalmology

Am J Ophthalmol

Ophthalmology

Ophthalmology

Ophthalmology

Two-year results of a randomized pilot study. Ophthalmology

Drusen and disciform macular detachment and degeneration

Arch Ophthalmol

Five-year incidence and disappearance of drusen and retinal pigment epithelial abnormalitiesWaterman study

Arch Ophthalmol

Risk factors for choroidal neovascularization in the second eye of patients with juxtafoveal or subfoveal choroidal neovascularization secondary to age-related macular degeneration

Arch Ophthalmol

The impact of the macular photocoagulation study

Results on the treatment of exudative age-related macular degeneration. Arch Ophthalmol

Treatment of Age-Related Macular Degeneration with Photodynamic Therapy(TAP) Study Group Verteporfin (Visudyne) therapy of subfoveal choroidal neovascularization in age-related macular degenerationone year results of two randomized clinical trials— TAP

Arch Ophthalmol

A model of the incidence and consequences of choroidal neovascularization secondary to age-related macular degenerationcomparative effects of current treatment and potential prophylaxis on visual outcomes in high-risk patients

Arch Ophthalmol

Photocoagulation of macular lesions

Trans Am Acad Ophthalmol Otolaryngol

Prophylactic photocoagulation of the fellow eye in exudative senile maculopathy

Mod Probl Ophthalmol

Treatment of drusen-related aging macular degeneration by photocoagulation

Trans Am Ophthalmol Soc

Photocoagulation of drusen-related macular degenerationa long-term outcome

Trans Am Ophthalmol Soc

Prophylactic perifoveal laser treatment of soft drusen

Aust N Z J Ophthalmol

A case of visual acuity loss following laser photocoagulation for macular drusen

Arch Ophthalmol

Laser photocoagulation to treat macular soft drusen in age- related macular degeneration

Retina

Original article
Predictors of drusen reduction after subthreshold infrared (810 nm) diode laser macular grid photocoagulation for nonexudative age-related macular degeneration☆