A Review of Micropulse Laser Photocoagulation

By Carolyn Majcher, O.D., and Andrew S. Gurwood, O.D., F.A.A.O., Dipl.

Goal Statement:

This article reviews the application and therapeutic efficacy of micropulse laser photocoagulation for the treatment of several devastating retinal conditions, including diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), venous occlusion and idiopathic central serious chorioretinopathy (ICSC).

Faculty/Editorial Board:

Carolyn Majcher, O.D., and Andrew S. Gurwood, O.D., F.A.A.O., Dipl.

Credit Statement:

This course is COPE-approved for 1 hour of CE credit. COPE ID is 32931-PS. Please check your state licensing board to see if this approval counts toward your CE requirement for relicensure.

Joint-Sponsorship Statement:

This continuing education course is joint-sponsored by the Pennsylvania College of Optometry.

Disclosure Statement:

Drs. Majcher and Gurwood have no relationships to disclose.

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GERMAN OPHTHALMOLOGIST GERD MEYER-SCHWICKERATH first pioneered retinal photocoagulation in the 1940s when he focused natural sunlight into the eye.^1,2 Using a heliostat (reflective concave mirror with a central viewing ocular), he constructed a functional sunlight photocoagulator.^1,3

Later in his career, Dr. MeyerSchwickerath assembled the first xenon-arc photocoagulator with Hans Littmann of Zeiss Laboratories in 1956.³ The first xenon-arc photocoagulator produced light comprised of various wavelengths within the visible and infrared spectrum.³ This beam produced destructive, full-thickness retinal burns.

Theodore Maiman, Ph.D., designed the first ophthalmic laser in 1960 at the Hughes Research Laboratory in Malibu, Calif.^1,3 It emitted monochromatic energy of 694nm.¹ Monochromatic lasers allowed tissue-specific photocoagulation, so certain layers of the retina could be targeted—particularly the retinal pigment epithelium (RPE).

Widespread use of ophthalmic laser photocoagulation began following the invention of the argon laser in 1968 by Francis L’Esperance, M.D.⁴ This platform used an ionized gas lasing medium.⁴

Today, the more commonly used Neodymium-doped yttrium aluminum garnet (Nd:YAG) and diode lasers use solid-state platforms that utilize crystals and semiconductors respectively.³ Modern laser models were introduced in the 1980s and have become popular because of their portability and ability to deliver laser in both continuous and pulse modes.³

This article reviews the application and therapeutic efficacy of micropulse laser photocoagulation for the treatment of several devastating retinal conditions, including diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), venous occlusion and idiopathic central serious chorioretinopathy (ICSC).

The Lowdown on Lasers

All lasers are comprised of three essential components: a lasing material, a pump source to introduce energy into the lasing material and an optical cavity with reflectors for light amplification.^5,6 Population inversion occurs when energy from the pump source is introduced into the lasing material, which excites electrons in the lasing material’s atoms and causes them to go from a steady, low-energy state to an unstable, higher-energy level.⁶

Decay (the return of electrons to the steady state energy level) stimulates the production of similarwavelength photons that have the ability to travel in phase as well as in the same direction.^6,7 Amplification occurs as photons travel back and forth in the optical cavity through the lasing material between a total reflecting mirror and a partial reflecting mirror.^6,7 When sufficient energy has built up, a burst of laser light is released through the partially reflecting mirror. Modifying various laser properties, such as spot size, duration, power and wavelength, creates specific target effects.³

An Overview of Laser Photocoagulation

Photocoagulation is accomplished through protein denaturation that is induced via absorption of radiant energy by the ocular chromophores.⁸ This process occurs mainly in the melanin of the RPE cells and choroidal melanocytes, where laser energy initially is converted into heat.⁵ A traditional laser burn creates a heat wave that spreads outward adjacently from the origin of the burn site in the RPE and/ or choroid.⁵ The ‘‘grayish-white’’ endpoint in conventional threshold photocoagulation signifies that the thermal wave has reached the overlying neurosensory retina with a temperature high enough to damage the natural transparency of the retina.⁵ As the transparency is altered, the light placed onto the retina becomes scattered, which creates the white appearance.⁵ This appearance typically is associated with a temperature rise of 20°C to 30°C above baseline body temperature.⁹ Inevitably, the thermal damage extends beyond the visible burn as collateral temperatures reach 10°C to 20°C above the baseline, contributing to the phenomenon of laser scar expansion over time.¹⁰

Collateral heat damage from threshold focal photocoagulation for DME causes significant side effects, including retinal scarring. Scars may enlarge progressively up to 300% and can cause significant vision decrease if the fovea becomes involved.¹¹ Whenever scarring replaces normal retinal architecture with gliotic/fibrotic matrix, irreversible damage to the overlying photoreceptors results.¹² Other potential side effects include the provocation of physiology, which promotes choroidal neovascularization (CNV), subretinal fibrosis and generalized loss of paraxial threshold sensitivity.^13-15

Similarly, panretinal photocoagulation (PRP) has been shown to cause a temporary loss in high spatial frequency contrast sensitivity, long-term visual acuity decrease in up to 10% of eyes, tritanopic color vision deficits, elevated dark adaptation threshold and generalized visual field constriction.^16-20 Patients have reported postoperative difficulty adjusting to dim and bright lighting, sorting dark colors, judging distances, negotiating stairways and avoiding obstacles.²¹

It is unlikely that the effect of conventional argon laser treatment is due to direct closure of retinal microaneurysms. Typically, closure of microaneurysms is delayed following therapy, with a closure rate of just 0.67% at twoweek follow-up.²² Even though closure is incomplete, significant reduction in macular thickness is observable and quantifiable on optical coherence tomography (OCT).²²

Biologic activities are thought to be the mechanisms by which laser photocoaglation works in sublethally injured RPE cells that surround areas of photocoagulation necrosis.²³ Laser photocoagulation has the ability to upregulate various biochemical mediators with antiangiogenic activity, such as pigment epitheliumderived growth factor (PEDF).²⁴ Additionally, laser stimulates the release of factors that increase angiotensin II and increase receptor activity, enabling inhibition of vascular endothelial growth factor (VEGF)-induced angiogenesis while decreasing VEGF inducers, such as transforming growth factor beta II.^25,26 Evidence suggests that decreased serum VEGF levels following PRP in eyes with PDR is likely secondary to a reduction in the tissue’s hypoxic drive.²⁷ The reduction in VEGF also reduces vascular permeability.²⁷

A typical PRP pattern of 1,200 to 1,500 burns of 0.5mm diameter may reduce the number of metabolically active photoreceptors as well as total oxygen consumption of the outer retina by approximately 20%.⁷ This reduction in the hypoxic state of the retina re-establishes a balance between retinal oxygen supply and demand. When the outer retinal oxygen consumption is dramatically decreased, oxygen from the choroid—which normally does not reach the inner retina— can now penetrate through the outer retina and compensate for the reduced retinal supply.⁷ Autoregulatory retinal arteriolar constriction follows the laserinduced reduction in inner retinal hypoxia, which likely induces a subsequent decrease in downstream capillary hydrostatic pressure and fluid leakage.^7,28

The predominant disadvantage to this modality is that it is destructive to viable tissue, which inevitably becomes a collateral casualty.

Retinal photocoagulation has a multitude of clinical applications, including the treatment of various ischemic, inflammatory and degenerative subretinal and intraretinal diseases.^29-36 In clinical application, photocoagulation has been effective at treating extrafoveal choroidal neovascular membranes secondary to age-related macular degeneration (AMD) and retinal ischemia.^29-36

Micropulse Laser Technology

Eight-hundred ten (810nm) micropulse diode laser treatment is a low-intensity procedure that is administered via high-density distribution in both pathologically involved and uninvolved areas of the retina.³⁷ This treatment was pioneered by Thomas R. Friberg, M.D., and associates in the late 1990s.³⁸

There are several commercially available 810nm micropulse lasers, including the OcuLight SLx (IRIDEX Corporation), IQ 810 (IRIDEX Corporation) and the FastPulse (Optos).

Micropulse photocoagulation technique divides the laser emission into a “train” of short, repetitive pulses that persist for 0.1 seconds to 0.5 seconds. The ‘‘on’’ time is the duration of each micropulse (typically 100μs to 300μs) and the ‘‘off’’ time (1,700μs to 1,900μs) is the interval between successive micropulses.^5,9 This “off” time allows for heat dissipation, which decreases collateral damage and confines treatment to the RPE.³⁷ This is in stark contrast to conventional continuous wave laser, where the same magnitude of energy is delivered throughout the entire exposure cycle of 0.1 seconds to 0.5 seconds.³

The duty cycle is calculated by taking the percentage of the period during which the laser is “on.” For example, with a duty cycle of 15% and a period of 1,000μs, the laser would be on for 150μs and off for 850μs (0.15=150/1,000). If the exposure time was set to 100,000μs, the laser would fire 100 repetitive pulses during that interval. The power and duty cycle are both adjustable, permitting the operator to vary the treatment intensity.⁵ When a low duty cycle is used, less heat is generated, allowing the RPE to return to baseline temperature before the next pulse is initiated. This eliminates cumulative thermal build-up.³⁷ Microscopic, isolated RPE photothermal damage can be achieved with laser powers as low as 10% to 25% of visible threshold powers.⁴²

Subthreshold micropulse diode laser photocoagulation (SMD) is designed to target the RPE melanocytes while avoiding photoreceptor damage.^5,12 The term “subthreshold” refers to photocoagulation that does not produce visible intraretinal damage or ophthalmically visible scarring either during or after treatment.⁹ In fact, burns are undetectable not only on clinical examination, but also on intravenous fluorescein angiography (IVFA) and fundus autofluorescene (FAF).³⁹ Intensity of subthreshold treatment can vary from no lesion produced to microscopic destruction of the RPE and photoreceptor outer segment structures.^40-42

Such selective tissue photocoagulation is not possible with long, continuous wave exposure times (50ms to 400ms).⁴³ Less collateral damage can be achieved by making the laser “on” time shorter than the thermal diffusion time.⁵ Due to the proximity of the RPE to the photoreceptors, very short laser exposures are required if the operator does not want the thermal wave to reach the neurosensory retina.^5,43 This lower energy treatment only denatures a small fraction of proteins without causing coagulation necrosis.³⁷

When the threshold of sublethal cellular injury is reached via the cumulative addition of denatured proteins, transcriptional activation of cytokine expression, release of growth factors and upregulation of matrix metalloproteinases occurs.^37,44 The same biologic activities that result from SMD treatment are induced indirectly by conventional threshold photocoagulation in sublethally injured RPE cells adjacent to the areas of the coagulation necrosis zone.^23,37

In addition to its advantage of decreased collateral damage over conventional argon laser photocoagulation, the absence of chorioretinal scaring allows for an overlapping application of burns that may extend into noninvolved areas of the retina.⁹ Frequent retreatment of involved retinal areas is also possible without fear of creating confluent retinal scarring.⁹ Also, because the transmission of near-infrared light through the cornea and lens is greater with an SMD laser than with the shorterwavelength lasers (e.g., Argon, Krypton), there is less pre-target light scatter, which permits treatment through dense, nuclear sclerotic cataracts.⁴⁵

Micropulse laser therapy is not free of disadvantages, however. The possibility of under-treatment is always a concern.⁴⁶ SMD treatment also seems to take longer to reach the same clinical endpoint as conventional continous laser, particularly when low-density application is used.⁵ For example, subtheshold micropulse panretinal photocoagulation (SMD PRP) induces a response that develops gradually, but without marked contraction of neovascular tissue.⁴⁵ Another limitation of SMD is that treatment protocols are not well established and there are no standards or dose-response clinical studies that outline specific combinations of pulse energy, duration and treatment density for ideal clinical responses.⁴⁶

Documentation of treated areas and inadvertent re-treatment of areas during a single session continue to be a problem. Because the modality delivers energy without leaving an observable fingerprint, it is incumbent on the surgeon to keep track of what has and has not been treated. One solution to this dilemma is indocyanine green angiography-assisted SMD photocoagulation.⁴⁷ SMD laser-treated areas appear dark from the resultant quenching of indocyanine green fluorescence.⁴⁷ Micropulse treatment can be angiographically documented to prevent inadvertent re-treatment as well as to aid in the planning of future therapy.^47,48

Diabetic Macular Edema

Perhaps the most widely used application of retinal laser therapy is focal and grid photocoagulation for the treatment of DME, which results when inner retinal hypoxia catalyzes the production of VEGF.⁷ When the pathologically produced VEGF overcomes the naturally produced inhibitor PEDF from the RPE, increased vascular permeability ensues, which causes the leakage of osmotically active molecules (retinal exudates) into the retinal tissues.⁷ These exudates siphon water from the capillaries, resulting in intraretinal edema.⁷ Additionally, hypoxic autoregulatory dilatation of the arterioles decreases resistance inside the vessels, indirectly increasing downstream capillary hydrostatic pressure.⁷ The result is fluid movement into the retinal tissues between the photoreceptors and the horizontal, bipolar and amicrine cells, yielding disorganization of the retina’s architecture and reduction of its ability to efficiently function as a light-gathering instrument. The outcome is variably reduced visual function.

The therapeutic effect of photocoagulation for DME was first documented in the Early Treatment of Diabetic Retinopathy Study (ETDRS) in 1979.⁴⁹ This landmark, randomized control trial included 754 eyes with macular edema and mild to moderate diabetic retinopathy.⁴⁹ Patients were randomly assigned to receive focal argon laser photocoagulation or deferral of photocoagulation.⁴⁹ Results showed that the combination of focal and grid laser photocoagulation yielded a reduction in the occurrence of moderate visual acuity loss by approximately 50% to 70% in eyes with retinal thickening or associated hard exudate formation that involved or threatened the center of the macula.⁵⁰

The treatment effect was most pronounced in eyes with clinically significant macular edema (CSME).⁴⁹ CSME was defined as a thickening of the retina at or within 500μm of the center of the foveola; hard exudates at or within 500μm of the center of the foveola; or a zone or zones of retinal thickening measuring one disc area or larger located within one disc diameter of the center of the foveola.⁴⁹

In the ETDRS, a pretreatment fluorescein angiogram was used to identify treatable lesions that were located between 500μm and two disc diameters of the center of the foveola. “Treatable lesions” included: discrete points of retinal hyperfluorescence or leakage (microaneurysms); areas of diffuse leakage within the retina (microaneurysms, intraretinal microvascular abnormalities or diffusely leaking retinal capillary beds); or large areas of hypofluorescence that were indicative of significant retinal avascular zones.⁴⁹

Focal leakage sites received 50μm to 100μm argon bluegreen (70% blue 488nm, 30% green 514.5nm) or green-only (514.5nm) burns of 0.1 seconds duration or less with enough power to achieve observable whitening.^3,49 For all microaneurysms greater than 40μm in diameter, the researchers attempted to obtain retinal whitening or darkening of the microaneurysm itself—even if repeated burns were necessary.⁴⁹ Treatment of lesions within 500μm of the foveola was recommended only if the visual acuity measured 20/40 and an intact perifoveal capillary network was present.⁴⁹ In these cases, the researchers recommended treatment of lesions up to 300μm from the center of the foveola.⁴⁹

The ETDRS researchers treated areas of diffuse leakage or nonperfusion in a grid pattern using moderate-intensity burns of 50μm to 200μm in size, spaced one burn-width apart.⁴⁹ They concluded that, for all eyes with CSME, focal photocoagulation should be considered to reduce the risk of additional visual loss; increase the chance of visual improvement; and decrease the possibility for chronic, persistent macular edema.⁴⁹

SMD photocoagulation of DME has gained momentum because of its association with an increase in central retinal sensitivity, as detected by microperimetry.³⁹ This is in comparison to a decrease within the central 12° of visual field in eyes treated with standard lasers as indicated in the modified ETDRS photocoagulation parameters.³⁹ The poor absorption of near infrared radiation by the yellow xanthophyll pigment of the macula may also allow for safer treatment administration closer to the center of the fovea.⁵¹

Three prospective, randomized clinical trials compared the results of the ETDRS or modified ETDRS protocols for conventional argon laser photocoagulation to SMD photocoagulation in eyes with CSME.^52,39,46

The first trial, conducted by João P. Figueira, M.D., and associates, included 84 previously untreated eyes with CSME secondary to type 2 diabetes mellitus that exhibited a best-corrected visual acuity of 20/80 or better.⁵² The patients were randomized to receive 810nm SMD photocoagulation or conventional argon laser treatment.

Results showed no statistical difference in visual acuity at one-year follow-up; however, there was a trend for better vision in the SMD group. Additionally, there was no significant difference in contrast sensitivity or central retinal thickness between the two groups at any point during follow-up.⁵²

The second trial, lead by Stela Vujosevicm, M.D., compared 810nm SMD photocoagulation with the modified ETDRS argon laser treatment protocol.³⁹ The study included 62 previously untreated eyes with CSME in patients with type 2 diabetes mellitus who exhibited foveal thickening of at least 250μm and a bestcorrected visual acuity of at least 20/200.

There was no significant difference in either visual acuity or central retinal thickness at oneyear follow-up between the two treatment groups.³⁹ The mean number of treatments was also similar (2.03 treatments in the SMD group vs. 2.1 treatments in the argon laser group). However, mean central 12° retinal sensitivity—as measured by microperimetry—increased significantly at one-year follow-up in the SMD group. In contrast, retinal sensitivity decreased significantly in the argon laser group.³⁹ Another measurement of general posterior segment health, FAF, remained unchanged in SMD-treated eyes, even after re-treatment. Conversely, all argon laser-treated eyes showed an increased number of FAF changes at one-month follow-up.³⁹

The third randomized clinical trial, conducted by Daniel Lavinsky, M.D., and associates, included 123 previously untreated eyes with CSME and retinal thickening within 500μm of the center of the foveola, a central retinal thickness of 250μm or greater and a best-corrected visual acuity that ranged between 20/40 and 20/400.⁴⁶ Eyes were randomized to one of three treatment groups: Modified ETDRS protocol argon laser photocoagulation; normaldensity 810nm SMD photocoagulation; or high-density 810nm SMD photocoagulation.

In both the normal-density and high-density subthreshold groups, the majority of the posterior pole including involved and uninvolved retinal areas was treated. In the normal-density SMD group, a grid of 125μm spots (300ms exposure duration and 15% duty cycle) spaced two burn-widths apart was applied.⁴⁶ In the highdensity group, the researchers confluently applied 125μm burns, with no attempt to specifically target or avoid microaneurysms.⁴⁶

Results showed that highdensity SMD photocoagulation was superior to the modified ETDRS treatment recommendation at one-year follow-up, while normal-density SMD eyes fared the worst.⁴⁶ There was no difference in postoperative central retinal thickness between the high-density SMD group and the modified ETDRS group at oneyear follow-up.⁴⁶ Approximately twice as many eyes experienced a gain of three or more lines in visual acuity at one year in the high-density SMD group (48%) compared to the modified ETDRS group (23%).⁴⁶

A non-comparative case series of 25 eyes utilized the longest documented follow-up period: three years.⁵¹ The researchers indicated that SMD photocoagulation had a beneficial, long-term effect on visual acuity improvement and resolution of CSME.⁵¹ At three years, just 8% of the patients experienced a three-line or greater loss in visual acuity.⁵¹ By the second year, CSME had completely resolved in 92% of eyes.⁵¹ Recurrent CSME was noted in 28% of patients by the third year. Accordingly, 24% of eyes received three sessions of SMD photocoagulation over the three-year period.⁵¹ Nevertheless, no detrimental side effects or scarring were associated with repeated treatment.⁵¹

Proliferative Diabetic Retinopathy

Panretinal photocoagulation, or scatter laser photocoagulation, is used for regressing cases of PDR as well as for treating intraretinal neovascularization secondary to any causative retinal pathology.²⁰

The Diabetic Retinopathy Study (DRS) indicated that PRP reduced the risk of severe visual loss (SVL), which was defined as visual acuity worse than 5/200.²⁰ SVL secondary to vitreo-proliferative retinopathy of any kind typically is the result of either vitreous hemorrhage or tractional retinal detachment.²⁰

In the DRS, treatment reduced the risk of SVL by approximately 50% for eyes with proliferative or severe nonproliferative diabetic retinopathy and visual acuity of 20/100 or better.²⁰ In particular, the DRS showed that the risk of developing SVL outweighed the risks of treatment side effects for eyes with PDR exhibiting high risk characteristics (HRC).²⁰ The HRC were defined as: eyes that exhibited intraretinal neovascularization on or within one disc diameter of the optic disc that equaled or exceeded 1/4 to 1/3 of a disc area in extent with or without vitreous hemorrhage or preretinal hemorrhage; or eyes with neovascularization and preretinal or vitreous hemorrhage with either neovascularization that measured less than 1/4 to 1/3 the size of the optic disc or neovascularization elsewhere that measured at least of a disc area.²⁰ Comparing only eyes with HRC, the rate of SVL was 49% in control eyes and 22% in treated eyes at five-year follow-up. ²⁰

The DRS argon treatment technique specified 800 to 1,600, 500μm burns of 0.1 seconds duration that extended to or beyond the vortex vein ampulae.²⁰ Focal treatment was recommended for neovascularization of the disc and retinal surface or elevated neovascularization elsewhere.²⁰ The researchers also recommended focal treatment for any microaneurysms or lesions thought to be causing macular edema before undergoing treatment for PDR.²⁰

Today, patients rarely receive focal treatment for neovascularization of the disc and elevated neovasculariztion elsewhere. In most cases, only scatter photocoagulation is completed, and treatment frequently is accomplished over two or more sessions.²⁰

Two major studies have investigated the benefits of SMD PRP. The first was a retrospective noncomparative review of 99 eyes with severe non-proliferative retinopathy or any degree of PDR that were treated with subthreshold 810nm micropulse PRP.⁴⁵ These subjects were followed for a mean duration of one year. Treatment was performed using a 500μm aerial spot size, 0.20 second exposure duration, and a 15% duty cycle with an initial power setting of 2,000mW.⁴⁵ All visible areas outside the major vascular arcades ranging to the retinal periphery were treated with a tight grid pattern.⁴⁵ The mean number of laser applications per session was 1,218. No patient complained of postoperative pain or loss of visual acuity, accommodation, night vision or visual field.

The researchers found that the overall visual acuity of treated subjects was unchanged compared to controls; however, eyes with a visual acuity of 20/30 or better increased from 39% to 48% during the course of the study.⁴⁵ The probability of vitreous hemorrhage at one year was 12.5% and the likelihood of vitrectomy was 14.6%.⁴⁵

The authors concluded that, compared to conventional PRP, the response to SMD PRP developed more gradually and without marked contraction of the neovascularization. They also determined that SMD PRP was useful in the management of eyes with extensive, active neovascularization that is more prone to retinal detachment following conventional PRP.⁴⁵

The second study was a prospective non-comparative case series of 13 eyes with PDR that were treated with 810nm SMD PRP. Initially, eyes were treated with 1,500 burns. Retreatment was performed as necessary at sixweek intervals thereafter.⁴³ Laser “on” time was 100μs to 300μs and “off” time was 1,700μs to 1,900μs within an exposure duration of 0.1s to 0.3s. Power was initially adjusted upward until a burn was barely visible and then adjusted to half that value for treatment. The overall number of burns required was approximately 5,250 over three to four treatment sessions, with an average response time of 13 weeks.³³ At six months, 62% of eyes showed complete regression of new vessels, 15% showed some regression and 23% showed no regression.⁴³

The authors concluded that satisfactory regression of new vessels was achieved using SMD PRP, although the technique required more burns than would be expected using the argon laser.⁴³ The numerous advantages of SMD PRP included absence of clinically visible laser scars, sparing of the neurosensory retina and photoreceptors in most cases, and the ability to treat larger areas of involved and uninvolved retina.⁴⁶ Having a decreased hemoglobin absorption profile, treatment is also more successful than conventional laser through preretinal fibrosis, vitreous hemorrhage and thin preretinal blood.⁴⁵ SMD PRP allowed for earlier treatment of neovascular retinal diseases given its lack of common side effects compared to conventional focal or pan retinal laser treatment.⁴⁵

Venous Occlusion

The Branch Retinal Vein Occlusion Study (BRVOS) indicated that grid argon laser photocoagulation improves the visual outcome of patients with 20/40 vision or worse who experienced debilitating macular edema three to eighteen months following the retinal venous occlusive event.³⁶ Of the treated eyes, 65% gained two or more lines from baseline and maintained that acuity for at least two consecutive visits, compared to 37% of control eyes.³⁶

One study compared the effect of SMD grid photoagulation to conventional threshold krypton grid photoagulation in 36 eyes with macular edema secondary to BRVO.⁴⁴ SMD treatment was performed using a 125μm spot size and a 0.2s exposure duration at 10% duty cycle.⁵³ Power was determined by means of a continuouswave test burn, which yielded a medium-white endpoint. In both treatment arms, treatment sites were spaced one burn-width apart and covered the entire area affected by macular edema.⁵³ The mean number of laser spots was greater in the SMD group (101 vs. 65), because the technique dictated high-density deployment.⁵³

Both groups demonstrated a reduced mean foveal thickness of half the original value. The result was achieved at six months in the standard laser group compared to one year for the SMD group.⁵³ After one year, there was no difference in mean foveal thickness or total macular volume between the two groups.⁵³ At 24-month follow-up, the researchers documented a visual acuity gain of three lines or more in 59% of patients in the SMD group compared to 26% of patients in the threshold group.⁵³ Visual acuity loss (three lines or more) at 24 months was similar between the two groups (12% in the SMD group and 10% in the threshold group).⁵³

Similar to the diabetic retinopathy experiments, these results confirm that while SMD treatment may take longer to achieve a similar reduction in edema compared to threshold treatment, long-term visual acuity gain is approximately two times more likely in treated eyes, where photoreceptors are spared.⁵³

An additional study showed that treatment with SMD grid photocoagulation, in combination with intravitreal triamcinolone injection, resulted in even better visual outcomes—91% of patients gained at least two lines of visual acuity at one-year follow-up.⁵⁴

To date, no clinical trials have documented the head-to-head efficacy of standard laser protocols vs. micropulse technique in the treatment of neovascularization secondary to BRVO. However, there is no gross pathophysiologic reason to assume that results for venous occlusive disease—or any other retinal vascular diseases that produce neovascularization—would be any different than those found in the PDR trials. Nevertheless, to ensure accuracy, the work needs to be completed.

Idiopathic Central Serous Chorioretinopathy

Idiopathic central serious chorioretinopathy (ICSC) is distinguished by a flat serous detachment of the neurosensory retina secondary to single or multiple serous RPE detachments, with or without areas of RPE atrophy.⁵⁵

Conventional laser photocoagulation is not normally indicated for ICSC, because it typically regresses spontaneously within several months.⁴⁷ It is only considered in specific cases, including persistent (four to six months) or progressive detachment (with or without inferior guttering); risk of permanent ICSC changes in the fellow eye; following multiple recurrences; or when an individual requires rapid visual recovery.⁴⁷ The treatment for these specific cases of ICSC is derived from multiple, randomized, controlled clinical trials, which have indicated that direct argon laser treatment to sites of leakage on IVFA has the potential to reduce disease duration without altering the final visual outcome.⁴⁷Additionally, treatment offers the potential to reduce the recurrence rate, particularly at the specific treatment site.^56,57

It is thought that the benefit of photocoagulation in ICSC is accomplished through occlusion of leaking defects in Bruch’s membrane and the adjacent RPE.⁵⁸ Photocoagulation induces stress on the contacted RPE cells, which promotes the proliferation and remodeling of RPE cells with new, healthy tight junctions, restoring the integrity of the outer blood-retinal barrier.^47,59 As photo-coagulation destroys the defective RPE barrier, non-proteinaceous subretinal fluid is drawn out rapidly by the oncotic pressure of the choroid. This process reduces fluid accumulation and promotes homeostasis.⁵⁹

One limitation of argon laser therapy for ICSC is that only extrafoveal sites are considered for treatment.⁶⁰ Treating affected juxtafoveal or subfoveal areas has the capability of enlarging existing central and paracentral scotomas created by the evolving pathologies.⁶⁰ Another side effect that has been reported is the development of CNV.⁵⁶ This phenomenon is more common when treatment is applied in closer proximity to the fovea.⁵⁶ Here, CNV is generated through a cytochemical response caused by laser-induced ruptures in Bruch’s membrane.⁶¹ The vulnerable tissues are particularly susceptible in the foveal region, where laser energy is absorbed in greater concentrations.⁶¹

Subthreshold micropulse photocoagulation has been implemented in cases of ICSC with chronic or persistent leakage.^47,60 In a prospective, non-comparative case series, researchers evaluated seven patients with chronic ICSC (unresolved after six months), persistent serous neuro-epithelial detachment, metamorphopsia, decreased visual acuity, and one or more active RPE leakage sites identified via IVFA. ⁴⁷

Photocoagulation using an SMD was initiated 15 minutes after the injection of indocyanine green dye, when staining of the RPE/Bruch’s membrane complex was visible.⁴⁷ Leakage sites were treated with a series of 50, 500ms exposures that were separated by 500ms pauses.⁴⁷ Each 500ms exposure delivered a train of 250 micropulses at 10% duty cycle, with a 112.5μm retinal spot size at 500mW of power.⁴⁷

Results suggested that, within two weeks following treatment, visual acuity and serous detachment improved in all seven patients.⁴⁷ Complete resolution of the serous neuro-epithelial detachment occurred within a median of six weeks in five patients, while the remaining two exhibited only a marked reduction.⁴⁷ At one year, the researchers noted no recurrence or worsening of the serous neuro-epithelial detachments or a decrease in visual acuity.⁴⁷

Another prospective consecutive case series included 26 eyes with ICSC juxtafoveal leakage that persisted for longer than four months. Eyes were divided into three groups based on IVFA findings: Point source leakage without associated RPE atrophy; point source leakage and associated RPE atrophy; and diffuse RPE decompensation without definite point source leakage.⁵¹ SMD was applied, dispensing approximately 100 exposures to each leaking site using an 810nm micropulse diode laser with 125μm spot size, 2ms exposure duration of 15% duty cycle and a mean power of 535mW.⁶⁰

In the first group, 83.3% of eyes experienced an improvement in visual acuity of three lines or greater, and all patients exhibited total reabsorption of subretinal fluid without recurrence after eight months of follow-up.⁶⁰ In the second group, 89% of eyes had total subretinal fluid reabsorption after one to three photocoagulation sessions, and 77.8% had an improvement in visual acuity of three lines or greater.⁶⁰ In the third group, 45% of eyes exhibited subretinal fluid reabsorption, with just 27% of those eyes gaining three or more lines of visual acuity at the end of the follow-up.⁶⁰ The remaining 55% of eyes required photodynamic therapy for final subretinal fluid reabsorption.⁶⁰ No eyes in any group developed laser-related scotomata, even after repeat treatment.⁶⁰

The authors concluded that SMD photocoagulation is effective in treating ICSC exhibiting point source leakage as identified by IVFA.⁶⁰ The authors noted that, in eyes with associated RPE atrophy or diffuse RPE decompensation, rapid recurrence is common and supplemental photodynamic therapy may be necessary.⁶⁰

SMD photocoagulation seems to offer a superior safety profile and appears to be as effective at treating numerous retinal conditions as conventional continuous wave argon laser photocoagulation.^9,12,43 The combination of budding micropulse delivery with radiation of various wavelengths is also groundbreaking, offering exciting new options in photocoagulation therapy for retinal disease.

Dr. Majcher is a primary care resident at the Eye Institute at Salus University in Elkins Park, Pa. Dr. Gurwood is professor of clinical sciences at the Eye Institute at Salus University.

References

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