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Micropulse laser therapy for DME

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Dr James Jabbour
MBBS BSc(Med) MPH FRANZCO
Director, Sydney Eye Specialists

Perhaps the most feared complication of macular laser treatment for experienced medical retina specialists is macular scarring and scar expansion over time. The latter may result in an increasing paracentral scotoma over many years and may potentially expand to involve the fovea. A tissue-sparing alternative to the standard modified Early Treatment of Diabetic Retinopathy Study (mETDRS) laser is ‘micropulse’ macular laser therapy.1

Micropulse laser therapy differs from standard laser as the continuous wave laser emission is ‘chopped’ into smaller ‘pulses’ over the same duration (Figures 1A–1D). For example, in a five per cent duty cycle, the laser emission is switched ‘on’ for 0.1 milliseconds and then switched ‘off’ for 1.9 milliseconds. This is repeated 100 times during a 200-millisecond treatment.

09 Figure 1A-F 09 Figure 1B-F
1A. Continuous wave laser exposure:
100 per cent duty cycle (DC)
1B. Micropulse high duty cycle
(15 per cent)
09 Figure 1C-F 09 Figure 1D-F
1C. Micropulse medium duty cycle
(10 per cent)
1D. Micropulse low duty cycle
(5 per cent)

Figure 1. Correlation between tissue ­temperature and laser duration

The cooling in the ‘off’ period prevents the temperature from reaching the threshold required to create a thermo-destructive burn. A concept similar to ‘pulse mode’ in phacoemulsification, in which the phaco-energy is divided into pulses, allowing cooling of the phaco-tip and preventing wound burn.

Retinal tissue is spared while maintaining the benefits of the photothermal stress response on the retinal pigment epithelium (RPE) and retina. The latter results in the induction of intracellular biological factors (PEDF,2 TSP1,3 SDF1 and B-Actin4), which play a role in anti-angiogenesis and the resolution of the macular oedema.

Does micropulse laser therapy work for diabetic macular oedema?

In short, yes. It has been shown to work as effectively as modified ETDRS laser in at least three randomised clinical trials. Vujosevic et al compared 810 nm micropulse laser with mETDRS in a randomised prospective trial on 62 eyes in 50 patients with diabetic macular oedema (DME).1 They demonstrated an equivalent stabilisation of vision and reduction in macular oedema in both treatment arms. However, in the ‘micropulse’ arm there was no evidence of RPE destruction on autofluorescence imaging and the retinal sensitivity improved rather than declined on microperimetry (p < 0.0001) (Figure 2A).

09 Figure 2A-F
Figure 2A. Modified ETDRS laser for diffuse diabetic macular oedema resulting in resolution of macular oedema at one year, but also in macular scarring which is seen on autofluorescence (seen on the right). The retinal sensitivity also declines post mETDRS laser at one year (top images).1
09 Figure 2B-F
Figure 2B. High density micropulse macular laser treatment also results in resolution of the diabetic macular oedema (see OCT); however, there is no evidence of retinal scarring on autofluorescence. The retinal sensitivity also improves after micropulse macular laser therapy (top images).1

In a prospective double blind controlled trial on 123 eyes, Lavinsky et al showed that contiguous or high-density micropulse therapy (no spacing between burns) was superior to low density and mETDRS guided laser at one year.5 The high-density group gained 12 letters on average compared to the four letters in the mETDRS group. Forty-eight per cent of patients in the high-density micropulse group gained =15 letters compared to 23 per cent in the mETDRS group. The average central macular thickness reduction at one year in the high density micropulse group was 154 µm compared to 126 µm in the mETDRS group.

Figueira et al (Oxford Group) also demonstrated comparable efficacy between micropulse diode laser and modified ETDRS at one year in a prospective randomised controlled trial involving 84 eyes in 53 patients.6

Is it safe?

Perhaps the greatest advantage of micropulse macular laser treatment is the minimal risk of macular scarring. In a long-term retrospective review of patients with DME or macular oedema related to branch retinal vein occlusion, Luttrull et al found no laser-induced retinal damage in patients treated with a five per cent duty cycle over a 10-year period.7 Fundus photos, infrared, autofluorescence, fluorescein and ICG angiography images were completely unremarkable and free of scarring.

Only eight per cent of the 10-15 per cent duty cycle micropulse patients experienced macular scarring similar to that of mETDRS macular laser. The study authors not only noted an absence of retinal scarring, but also an improvement in retinal sensitivity post micropulse laser treatment, which correlated with the resolution of the macular oedema1 (Figure 2B).

By comparison, the modified ETDRS group experienced a decline in retinal sensitivity, with the macular scars being visible on autofluorescence (Figure 2B). In Figure 3, macular scarring from ETDRS grid laser has expanded to involve the fovea and has resulted in long-term irreversible central visual loss—a risk that is significantly reduced by micropulse macular laser therapy. With micropulse laser, treatment may be applied much closer to the fovea without the fear of creating a scar and correlating central scotoma which expands over time.

09 Figure 3-F
Figure 3. Traditional ETDRS grid laser resulting in late-stage macular scar expansion and loss of central vision

A 37-year-old accountant with long-standing type 1 diabetes presents with slightly blurred vision in his right eye over the previous two months. He had a myocardial infarction six months prior to the appointment. He also has hypertension and hyperlipidaemia. He is a non-smoker, has no renal impairment, and his most recent glycaemic control has improved (HBA1c 7.0 per cent).

On examination, his visual acuity is reduced to BCVA 6/9 OD and 6/6 OS. Fundoscopy reveals multiple microaneurysms in close proximity to both foveae in association with clinically significant diabetic macular oedema. In the right eye the macular oedema is foveal-involving (Figure 4).

09 Figure 4-F
Figure 4. Right foveal-involving clinically significant  macular oedema

There is background moderate non-proliferative diabetic retinopathy bilaterally. Early and late frames on fluorescein angiography confirm the presence of multiple leaking microaneurysms and the fovea-involving macular oedema (Figures 5A and 5B). There is minimal macular ischaemia on fluorescein angiography. After a discussion of the treatment options, he declines intravitreal anti-VEGF therapy. He is concerned about the theoretical risk to his cardiac health posed by repeated anti-VEGF injections, particularly in light of his recent myocardial infarction.

09 Figures 5A And 5B-F
Figures 5A and 5B. Early and late phases of the fluorescein angiogram confirming leakage from multiple peri-foveal microaneurysms and DME

After consent is obtained, confluent 577 µm yellow micropulse laser with a five per cent Duty Cycle8 is applied to the oedematous macular area. The macular oedema slowly resolves and four months later his visual acuity improves to 6/6 in the right eye. OCT examination at four months demonstrates mild residual macular oedema confined to the inner retina (Figure 6). This residual macular oedema continues to resolve and is managed conservatively.

09 Figure 6-F
Figure 6. Resolution of DME four months post right micropulse macular laser therapy

This case demonstrates that micropulse laser therapy may be applied close to the fovea without the fear of central scarring and scotoma. It is particularly useful in patients in whom there is a contraindication to anti-VEGF therapy and who have either centre-involving diabetic macular oedema or clinically-significant macular oedema threatening the fovea.

Summary

Micropulse macular laser is an evidence-based, repeatable and safe treatment for diabetic macular oedema. Relative to standard modified ETDRS laser, there is less risk of macular scarring, scotoma, and scar expansion over time. The retinal sensitivity is also preserved in micropulse laser, whereas it is reduced after standard modified ETDRS laser treatment for DME.

It is a useful adjunct to intravitreal anti-VEGF therapy and is particularly useful in foveal-sparing clinically significant macular oedema or in patients in whom there is a contraindication to anti-VEGF therapy. The reduced risk of macular scarring allows treatment closer to the fovea than with standard mETDRS laser. Micropulse laser is also useful in other retinal disorders such as branch retinal vein occlusion and central serous chorioretinopathy.

Micropulse laser is another major step in the natural evolution to more refined and less destructive treatments for diabetic macular oedema.

 

  •  Dr Jabbour uses an Iridex Micropulse laser supplied by OptiMed

 

  1. Vujosevic S, Bottega E, Casciano M, Pilotto E, Convento E, Midena E. Microperimetry and fundus autofluorescence in diabetic macular edema: subthreshold micropulse diode laser versus modified early treatment diabetic retinopathy study laser photocoagulation. Retina 2010; 30: 6: 908-916.
  2. Ogata N, Tombran-Tink J, Jo N, Mrazek D, Matsumura M: Upregulation of pigment epithelium-derived factor after laser photocoagulation. Am J Ophthalmol 2001; 132: 3: 427-429.
  3. Binz N, Graham CE, Simpson K, Lai YK, Shen WY, Lai CM, Speed TP, Rakoczy PE. Long-term effect of therapeutic laser photocoagulation on gene expression in the eye. FASEB J 2006; 20: 2: 383-385.
  4. Yu AK, Merrill KD, Truong SN, Forward KM, Morse LS, Telander DG. The comparative histologic effects of subthreshold 532- and 810-nm diode micropulse laser on the retina. Invest Ophthalmol Vis Sci 2013; 54: 3: 2216-2224.
  5. Lavinsky D, Cardillo JA, Melo LA Jr, Dare A, Farah ME, Belfort R Jr. Randomized clinical trial evaluating mETDRS versus normal or high-density micropulse photocoagulation for diabetic macular edema. Invest Ophthalmol Vis Sci 2011 Jun 17; 52: 7: 4314-4323.
  6. Figueira J, Khan J, Nunes S et al. Prospective randomised controlled trial comparing sub- threshold micropulse diode laser photocoagulation and conventional green laser for clinically significant diabetic macular oedema. Br J Ophthalmol 2009; 93: 10: 1341-1344.
  7. Luttrull JK, Sramek C, Palanker D, Spink CJ, Musch DC. Long-term safety, high-resolution imaging, and tissue temperature modelling of subvisible diode micropulse photocoagulation for retinovascular macular edema. Retina 2012; 32: 2: 375-386
  8. Iridex IQ 577 Laser System


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