Laser Photocoagulation of Drusen

Number: 0609

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses laser photocoagulation of drusen.

1. Experimental and Investigational

   Aetna considers laser photocoagulation (including sub-threshold laser photocoagulation) of macular drusen experimental and investigational for the prevention and treatment of age-related macular degeneration because it has not been shown to be effective and may be associated with loss of visual acuity.

2. Related Policies

   • CPB 0701 - Vascular Endothelial Growth Factor Inhibitors for Ocular Indications

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
CPT codes not covered for indications listed in the CPB:
67220	Destruction of localized lesion of choroid (eg, choroidal neovascularization); photocoagulation (eg, laser), 1 or more sessions [sub-threshold laser photocoagulation of macular drusen]
ICD-10 codes not covered for indications listed in the CPB (not all-inclusive):
H31.101 - H31.109	Choroidal degeneration, unspecified
H31.111 - H31.119	Age-related choroidal atrophy
H31.121 - H31.129	Diffuse secondary atrophy of choroid
H35.30 - H35.3293	Age-related macular degeneration
H35.361 - H35.369	Drusen (degenerative) of macula
H47.321 - H47.329	Drusen of optic disc

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Background

Drusen are deposits located deep in the sensory retina that are seen characteristically in eyes with age-related macular degeneration (ARMD).  As multiple large drusen are a risk factor for the development of visual loss from ARMD, laser strategies to cause drusen to resorb have been devised.  Studies that have been performed thus far have been small and short-term.  Two large, randomized controlled trials (RCTs) using laser photocoagulation prophylactically for the treatment of ARMD are underway to determine the efficacy of such treatment.

In an update of a pilot RCT on the use of laser treatment in eyes with large drusen, it was found that throughout 4 years of follow-up, there were no statistically significant differences in change in visual acuity (VA), contrast threshold, critical print size, or incidence of geographic atrophy.  With additional follow-up, the large increase in the incidence of choroidal neovascularization observed within 18 months of treatment was maintained; however, by 30 months, the incidence in the 2 treatment groups was the same.  Most drusen resolution in treated eyes occurred within 24 months of the initial treatment.  Treated eyes that received higher-intensity laser burns had an increased risk of choroidal neovascularization.  Among eyes developing choroidal neovascularization in each treatment group, most lesions (2/3 or more) were composed of occult neovascularization only.  It was concluded that laser treatment as applied in the Choroidal Neovascularization Prevention Trial (CNVPT) caused an excess risk of choroidal neovascularization in the first year or so after treatment.  The increased early incidence of choroidal neovascularization was not associated with either a harmful or beneficial effect in this pilot study (CNVPT, 2003).

Furthermore, in an interim report of the Drusen Laser Study (DLS) on the use of laser photocoagulation in treating high-risk age-related maculopathy, Owens et al (2003) noted that there were 156 patients included in the interim analysis, and timed information was available on 153.  Choroidal revascularization (CNV) occurred in 21 of 81 (26 %) patients in the treatment group and in 13 of 75 (17 %) patients in the no treatment group (p = 0.19).  Visual acuity loss at 2 years occurred in 9 of 54 (17 %) patients in the treatment group compared to the 2 of 48 (4 %) patients in the no treatment group (p = 0.056).  The authors stated that they were only the second group to identify possible laser-induced CNV despite other similar studies in progress.  Equipoise of the DLS investigators was lost, and recruitment was halted.

Ruiz-Moreno et al (2003) stated that macular atrophy can occur after green argon laser photocoagulation of soft drusen.  The development of macular atrophy was associated with a significant decrease in best-corrected VA (BCVA).

Bylsma and Guymer (2005) stated that established treatments for ARMD include argon laser photocoagulation of extra-foveal CNV and photodynamic therapy of selected sub-foveal CNV.  Newer approaches are targeting the angiogenic pathway in CNV development.  Currently, other treatment modalities, such as radiotherapy and transpupillary thermotherapy do not have a clear role to play.  Surgical options are experimental and only available in some centers for selected patients.  Prevention of ARMD remains elusive.  Dietary supplements may have a role, while statins and prophylactic laser photocoagulation of drusen remain experimental.

Figueroa et al (2006) stated that presently it is unclear if removal of drusen after photocoagulation is beneficial to the patients.  In a non-randomized non-masked clinical study, Nili-Ahmadabadi et al (2007) examined the effect of prophylactic sub-threshold laser macular grid photocoagulation on drusen area and assessed the visual outcome and incidence of choroidal neovascularization in patients with soft drusen maculopathy.  A total of 18 patients (36 eyes) with bilateral soft drusen maculopathy were studied.  For each patient, 1 eye was treated with 48 sub-threshold (invisible end-point) applications of 532-nm KTP-laser in a macular grid pattern and the fellow eye was observed.  Soft drusen areas were calculated and compared between the 2 groups at baseline and follow-up visits at 3, 6, 12, and 30 months of therapy.  Best corrected visual acuity was also compared in observed and laser-treated eyes.  Reduction of drusen area, change in VA, and rate of CNV were assessed in both groups.  At baseline, there was no significant difference in the mean drusen surface area between the 2 groups (p = 0.90).  The mean surface area of soft drusen in treated eyes was 6.51 mm(2) after 30 months and 7.58 mm(2) (p = 0.50) in the control eyes.  There was a trend towards reduction in the mean soft drusen area after 30 months from baseline in laser-treated eyes (6.51 versus 6.97 mm(2)).  In treated eyes, there was no statistically significant difference between the mean BCVA at the baseline (0.28 logMAR) and after 30 months (0.32 logMAR) (p = 0.40).  The authors concluded that sub-threshold macular grid photocoagulation with 532-nm KTP-laser did not seem to reduce drusen surface area significantly and did not improve BCVA after 30 months.

In a Cochrane review, Parodi and colleagues (2009) examined the effectiveness and adverse effects of laser photocoagulation of drusen in ARMD.  Randomized controlled trials of laser treatment of drusen in ARMD in which laser treatment had been compared with no intervention or sham treatment were selected.  Two types of trials were included.  Some trials studied 1 eye of each patient (unilateral studies); other studies recruited patients with bilateral drusen and randomized 1 eye to photocoagulation or control and the fellow eye to the other group.  Two review authors independently selected studies and extracted data.  Data were pooled from unilateral and bilateral studies using a random-effects model.  For the bilateral studies, these researchers estimated the within-patient correlation coefficient from 1 study and assumed it was valid for the others.  They found 9 studies that randomized 2,216 people: 4 unilateral trials, 3 bilateral trials and 2 trials that included both a unilateral and a bilateral study arm.  Overall, the studies were of moderate quality.  Only half of the trials reported adequate allocation sequence generation, allocation concealment and masking of VA outcome assessors.  Although 2 (of the 9) studies reported significant drusen disappearance at 2 years, photocoagulation did not appear to affect the development of CNV at 2 years follow-up (9 studies, 1,767 people followed-up, odds ratio (OR) 1.04, 95 % confidence interval [CI]: 0.71 to 1.51) or the loss of 3 or more lines of visual acuity (6 studies, 1,628 people followed-up, OR 1.17, 95 % CI: 0.75 to 1.82).  The authors concluded that the trials included in this review confirm the clinical observation that laser photocoagulation of drusen leads to their disappearance.  However, there is no evidence that this results in a reduction in the risk of developing CNV, geographic atrophy or VA loss.

A review of treatment for age-related macular degeneration in BMJ Clinical Evidence concluded that the effectiveness of laser to drusen is unknown (Arnold & Heriot, 2006). The authors stated that we don't know whether laser treatment of drusen prevents progression of disease, and it may increase short-term rates of choroidal neovascularisation.

Friberg and colleagues (2009) determined the prophylactic and therapeutic value of a single sub-threshold 810-nanometer laser treatment in patients with high-risk drusen as a manifestation of dry ARMD in both eyes.  This study enrolled 1,278 eyes of 639 subjects who were 50 years or older with at least 5 drusen 63-microm or more in diameter in each eye.  Treatment consisted of the placement of an annular grid of 48 extra-foveal, sub-threshold 810-nm diode laser applications centered at but sparing the foveola in 1 eye of each subject, with the fellow eye serving as a control.  Development of choroidal neovascularization and change in BCVA were compared between treated and untreated eyes.  Sub-threshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes.  A modest VA benefit in treated eyes was found at 24 months (1.5 letter difference; p = 0.04) and in the treated eyes of subjects with a baseline VA between 20/32 and 20/63 (4.0 letter difference; p = 0.0034).  However, this treatment effect was not sustained at 3 years.  The authors concluded that a single sub-threshold 810-nanometer laser treatment to eyes of patients with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization.

Mojana et al (2011) examined the long-term effect of subthreshold diode laser treatment for drusen in patients with non-exudative ARMD with spectral domain optical coherence tomography (OCT) combined with simultaneous scanning laser ophthalmoscope.  A total of 8 eyes of 4 consecutive ARMD patients with bilateral drusen previously treated with subthreshold diode laser were imaged with spectral domain OCT/scanning laser ophthalmoscope.  Abnormalities in the outer retinal layers' reflectivity as seen with spectral domain OCT/scanning laser ophthalmoscope were retrospectively analyzed and compared with color fundus pictures, and autofluorescence images were acquired immediately before and after the laser treatment.  A focal discrete disruption in the reflectivity of the outer retinal layers was noted in 29 % of the laser lesions.  The junction in between the inner and outer segment of the photoreceptor was more frequently affected, with associated focal damage of the outer nuclear layer.  Defects of the retinal pigment epithelium were occasionally detected.  These changes did not correspond to threshold burns on color fundus photography but corresponded to focal areas of increased autofluorescence in the majority of the cases.  The authors concluded that subthreshold diode laser treatment causes long-term disruption of the retinal photoreceptor layer as analyzed by spectral domain OCT/scanning laser ophthalmoscope.  The concept that subthreshold laser treatment can achieve a selected retinal pigment epithelium effect without damage to rods and cones may be flawed.

Huang et al (2011) prospectively evaluated the safety and effectiveness of prophylactic laser treatment in Chinese patients with bilateral soft drusen; these researchers examined the structure and function of the macula 8 years after treatment.  A total of 10 patients with more than 10 soft drusen (greater than 125 mm) and BCVA greater than or equal to 20/25 in each eye participated in the study.  One eye, with relatively more drusen, was exposed to an argon laser (514 nm) to achieve a barely visible retinal lesion.  The contralateral eye was used as a control.  Fluorescein angiography, Amsler tests, Fourier-domain OCT and visual evoked potential tests were carried out 8 years later.  No choroidal neovascularization was seen in the laser-treated eyes or control eyes.  There were no significant differences in visual acuity or P100 latency and amplitude between the laser treated eyes and contralateral eyes (t = 1.685, 1.184; p > 0.05).  The thickness of the retinal pigment epithelium of the treated eyes was less than that of the contralateral eyes (t = -4.540; p < 0.05).  The full retinal thickness in treated eyes was slightly, but insignificantly, reduced relative to contralateral eyes (t = -1.746; p > 0.05).  The authors concluded that the treatment was associated with a reduction in retinal pigment epithelium thickness elevation compared with the contralateral eyes; macular function was not impaired.

In a prospective, interventional case-series study, Lenassi and colleagues (2013) examined if laser treatment to the retinal pigment epithelium anterior to drusen in eyes of patients with EFEMP1-related maculopathy affects visual acuity, deposit volume, and retinal sensitivity.  In 11 patients with autosomal dominant drusen and confirmed disease-causing EFEMP1 mutation, the worse-seeing eye was treated with Argon green laser (10 to 15 laser spots; 200-μm spot size, 0.1-second duration, 80 to 120 mW).  Patients were examined before treatment and 1, 3, 6, and 12 months after the procedure.  Clinical assessment included VA, fundus-controlled perimetry, spectral-domain OCT, and auto-fluorescence imaging.  Custom-made software allowed for co-registration of fundus-controlled perimetry and spectral-domain OCT data sets.  The main outcome measures were change in VA, retinal sensitivity, and drusen volume.  The untreated eyes lost an average of 0.8 letters, whereas the treated eyes gained an average of 4.9 letters.  For fundus-controlled perimetry, locus-by-locus differences in sensitivity were calculated between pre-treatment and post-treatment assessments; subsequently, the overall difference in the treated and untreated eye was compared.  Five patients showed significant improvement in retinal sensitivity, 5 patients showed no change, and 1 patient showed significant deterioration.  An increase in mean drusen thickness was observed in the untreated eyes, but not in the treated eyes (p = 0.0322).  The thickness of the drusen correlated with retinal sensitivity (ρ = -0.49; p < 0.0001).  Safety was demonstrated and no adverse events were observed.  The authors concluded that low-energy laser treatment is safe and may be effective in the treatment of autosomal dominant drusen.  Moreover, they stated that further evaluation with long-term assessment is needed to confirm the benefits.

In a Cochrane review, Virgili et al (2015) examined the effectiveness and adverse effects of laser photocoagulation of drusen in ARMD. These investigators searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2015, Issue 7), Ovid Medline, Ovid Medline In-Process & Other Non-Indexed Citations, Ovid Medline Daily, Ovid OldMedline (January 1946 to August 2015), Embase (January 1980 to August 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2015), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) .  These researchers did not use any date or language restrictions in the electronic searches for trials.  They last searched the electronic databases on August 3, 2015.  Randomized controlled trials of laser treatment of drusen in ARMD in which laser treatment had been compared with no intervention or sham treatment.  Two types of trials were included.  Some trials studied 1 eye of each participant (unilateral studies); other studies recruited participants with bilateral drusen and randomized 1 eye to photocoagulation or control and the fellow eye to the other group.  Two review authors independently selected studies and extracted data.  The authors pooled data from unilateral and bilateral studies using a random-effects model.  For the bilateral studies, these researchers estimated the within-person correlation coefficient from 1 study and assumed it was valid for the others.  The update of this review found 2 additional studies, totaling 11 studies that randomized 2,159 participants (3,580 eyes) and followed them up to 2 years, of which 6 studies (1,454 participants) included people with 1 eye randomized to treatment and 1 to control.  Studies were conducted in Australia, Europe and North America.  Overall, the risk of bias in the included studies was low, particularly for the larger studies and for the primary outcome development of CNV.  Photocoagulation did not reduce the development of CNV at 2 years' follow-up (OR 1.07, 95 % CI: 0.79 to 1.46, 11 studies, 2,159 participants (3,580 eyes), high quality evidence).  This estimate meant that, given an overall occurrence of CNV of 8.3 % in the control group, these investigators estimated an absolute risk reduction by no more than 1.4 % in the laser group, according to the lower CI limit.  Only 2 studies investigated the effect on the development of geographic atrophy and could not show a difference, but estimates were imprecise (OR 1.30, 95 % CI: 0.38 to 4.51, 2 studies, 148 participants (148 eyes), low quality evidence).  Among secondary outcomes, photocoagulation led to drusen reduction (OR 9.16, 95 % CI: 6.28 to 13.4, 3 studies, 570 participants (944 eyes), high quality evidence) but was not shown to limit loss of 3 or more lines of VA (OR 0.99, 95 % CI: 0.81 to 1.22, 9 studies, 2,002 participants (2,386 eyes), moderate quality evidence).  In a subgroup analysis, no difference could be shown for conventional visible (8 studies) versus sub-threshold invisible (4 studies) photocoagulation for the primary outcomes (p value = 0.29).  The effect in the sub-threshold group did not suggest a relevant benefit (OR 1.27, 95 % CI: 0.82 to 1.98).  No study used micro-pulse sub-threshold photocoagulation.  No other adverse effects (apart from development of CNV, geographic atrophy or visual loss) were reported.  The authors concluded that the trials included in this review confirmed the clinical observation that laser photocoagulation of drusen led to their disappearance.  However, treatment did not result in a reduction in the risk of developing CNV, and was not shown to limit the occurrence of geographic atrophy or VA loss.  They stated that ongoing studies are being conducted to examine if the use of extremely short laser pulses (i.e., nanosecond laser treatment) cannot only lead to drusen regression but also prevent neovascular ARMD.

Conjunctival Papilloma

Belfort and colleagues (2018) evaluated the safety and 1-year effect of pattern scanning laser photocoagulation treatment for pedunculated papillomatous and sessile conjunctival lesions in a low-resource setting with extremely limited operating room access.  Adult patients with clinical diagnosis of conjunctival papilloma underwent complete ophthalmologic examination including anterior segment photography.  After topical anesthesia and toluidine blue 1 % instillation, the lesion was treated by pattern scanning photocoagulation using a duration time that varied from 20 to 100 ms and power from 600 to 1,800 mW, treating the entire lesion surface with a 2-mm margin.  Patients were examined weekly for a month then monthly and underwent re-treatment as necessary.  A total of 6 patients (7 eyes) who had clinically significant non-malignant pedunculated or sessile papillomatous lesions were treated.  All lesions responded to treatment, with complete resolution after an average of 2.3 sessions.  Procedures were well-tolerated with only mild discomfort persisting up to 2 days post-treatment.  Patients were monitored for a mean follow-up time of 13 months with no recurrences reported.  The authors concluded that short-term results of the pattern scanning laser photocoagulation approach, with toluidine blue for papillomatous conjunctival lesions were favorable with a 100 % success rate in this cohort.  This rate was comparable to surgical excision.  This novel strategy proved to be a less resource intensive alternative that not only could demonstrate its usefulness in settings with chronic operating room shortages, but also in recurrent cases.  Moreover, they stated that longer follow-ups with a larger sample size and cost-analysis are needed to confirm these findings.

Macular Edema Secondary to Retinal Vein Occlusion

In a pilot study, Feng and colleagues (2018) evaluated the safety and efficacy of combined anti-vascular endothelial growth factor (VEGF) agents, oral glucocorticoid, and laser photocoagulation therapy for the treatment of macular edema (ME) secondary to retinal vein occlusion (RVO).  This trial included 16 eyes of 16 patients with RVO-associated ME.  Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent; 2 weeks later, patients underwent standard laser photocoagulation; BCVA, central retinal thickness (CRT), and retinal vessel oxygenation were examined over 12 months.  Patients received 1.43 ± 0.81 anti-VEGF injections.  Mean baseline and 12-month logMAR BCVA were 0.96 ± 0.51 (20/178) and 0.31 ± 0.88 (20/40), respectively, in eyes with central RVO (CRVO) (p < 0.00), and 1.02 ± 0.45 (20/209) and 0.60 ± 0.49 (20/80), respectively, in eyes with branch RVO (BRVO) (p < 0.00). At 12 months, CRT had significantly decreased in eyes with CRVO (p < 0.00) and BRVO (p < 0.00).  Venous oxygen saturation had significantly increased in eyes with CRVO (p < 0.00) and BRVO (p < 0.00).  No examined parameters were significantly different between the 2 RVO groups; and no serious adverse effects (AEs) occurred.  The authors concluded that anti-VEGF, glucocorticoid, and laser photocoagulation combination therapy improved visual outcome, prolonged therapeutic effect, and reduced the number of intravitreal injections in eyes with RVO-associated ME.

The authors stated that this study had several drawbacks.  First, the small sample size (n = 16 eyes) of this pilot study limited the statistical significance of observed changes and differences between patients with BRVO and CRVO.  Second, though it was prospective, this study was not randomized, controlled, or masked.  Third, oral glucocorticoid dose was tailored to each patient for safety reasons.  This may have confounded these findings because of varying steroid effects among patients.  Therefore, these findings should be validated with future multi-center, randomized, controlled studies on a larger number of patients.  These studies should also standardize the timing and dose of all therapies administered.

Polypoidal Choroidal Vasculopathy

In a case-report, Sheth and associates (2018) described management of residual branch vascular network (BVN) in a 64-year old woman with polypoidal choroidal vasculopathy (PCV) by thermal laser photocoagulation of feeder vessel.  Subject exhibited moderate response to 7 doses of intravitreal ranibizumab, 6 doses of intravitreal bevacizumab and 1 session of photodynamic therapy (PDT).  The patient has resolved polyps but persistence of disease activity due to residual BVN and large pigment epithelial detachment (PED).  Patient underwent thermal laser photocoagulation of feeder vessel of BVN identified on indocyanine green angiography (ICGA).  There was complete resolution of residual BVN and large PED, which was confirmed on ICGA.  The authors concluded that recalcitrant cases of PCV without polyps but having BVN with feeder vessel can be managed by ICGA-guided thermal laser photocoagulation.  They stated that this case report showed the importance of utilizing multi-modal imaging such as ICGA for identification of feeder vessel and its deployment for optimal management of refractory PCV.  The findings of this single-case study need to be validated by well-designed studies.

Retinoschisis

Schwarze et al (1990) reported on 2 cases with a special form of senile retinoschisis with retinal detachment.  In both cases, a typical retinoschisis was combined with a giant tear of the outer retinal layer and a sickle-shaped retinal detachment extending almost to the macula.  In contrast to previously published cases, which were treated by a conventional scleral buckling procedure or vitrectomy with fluid air exchange, it was decided to demarcate the retinal detachment by argon laser photocoagulation.  The authors considered this non-invasive procedure sufficiently safe and effective.

Selaru et al (2000) noted that retinoschisis is a vitreo-retinal dystrophy characterized by splitting of the neuro-retinal layers.  The authors presented 2 cases of retinoschisis associated with retinal detachment.  In particular, 1 patient was diagnosed with von Willebrand disease and the other one, with oto-mandibular dysostosis (Francois-Haustrade).  The authors presented therapeutic methods used in this 2 cases – laser argon photocoagulation, trans-scleral cryopexia, scleral buckling and also the functional and anatomical results.

Gopal et al (2001) report a case of progressive congenital retinoschisis is where the schisis cavity collapsed following argon laser photocoagulation.  Despite reports to the contrary, the authors felt that in the absence of significant vitreous or inner layer traction, photocoagulation applied as light burns in the schisis cavity may be beneficial in collapsing the cavity.  Whether or not this collapse of the schisis cavity reduced the risk of rhegmatogenous retinal detachment is unclear.

Malagola et al (2002) provided a detailed description of the clinical features that are considered fore-runners of symptomatic complications in asymptomatic degenerative retinoschisis, and showed that in selected cases at this stage prophylactic photocoagulation may be a better choice than mere observation.  A total of 43 eyes of 27 patients with asymptomatic bullous degenerative retinoschisis and outer layer breaks (OLBs) were studied through binocular indirect dynamic ophthalmoscopy and retinal biomicroscopy with the Goldmann 3-mirror lens, fundus drawings, and photographs where feasible.  Argon laser treatment was carried out on each eye: first, around the posterior border of the schisis to achieve a full-thickness retinal scar, and then on the schisis itself to promote scarring of the retinal pigment epithelium, thus avoiding retinal detachment.  The follow-up was 2 years minimum after treatment.  OLBs usually involved the largest schises when multiple retinal splittings were present.  Breaks were single in 18 eyes (peripheral in 16 and posterior in 2) and multiple in 25 (peripheral in 15 and posterior in 10).  Overall, 23 eyes showed asymptomatic retinal detachment (schisis detachment): 20 with peripheral outer layer breaks and 3 with posterior breaks.  Schisis detachment was localized to the schisis area in the first group, whereas it extended beyond the posterior boundary of retinoschisis in the latter.  After treatment, no posterior progression of retinoschisis was noted nor did symptomatic retinal detachment arise.  Only 1 eye had complications in the second step of the treatment that was later resolved with medical care.  The authors concluded that prophylactic Argon laser photocoagulation can be used safely in the asymptomatic stage of bullous retinoschisis with outer layer breaks to avoid the onset of acute symptomatic retinal detachment.

Moreno-Lopez et al (2012) described a case of maculopathy consisting of macular retinoschisis and serous macular detachment occurring in a patient with an acquired enlarged optic disc cup, similar to the maculopathy observed in congenital optic nerve abnormalities, mainly optic nerve pits and colobomas, without vitreo-macular traction nor angiographic leak.  Pars plana vitrectomy with argon laser endophotocoagulation and gas tamponade was found to be useful.  Traction from membranes covering deep optic disc cups may create small retinal dehiscences, as described in congenital optic nerve abnormalities, which will enable the liquefied vitreous to pass, leading to retinoschisis with or without associated neurosensory detachment.  Vitrectomy, photocoagulation, and gas tamponade may be a useful therapy for this entity.

In summary, there is insufficient evidence to support the use of argon laser photocoagulation for the treatment of retinoschisis.

Sub-Threshold Laser Photocoagulation for the Prevention and Treatment of Age-Related Macular Degeneration

Querques and co-workers (2018) provided an updated review of laser approaches to non-exudative ARMD.  PubMed and Medline database searches were performed using the terms "laser" and "photocoagulation" associated with "age-related macular degeneration", and latest publications up to May 2017 had been reviewed.  Moreover, the design of an ongoing single-center, non-randomized, phase I to II, pilot study, the PASCAL-GA trial, coordinated by F. Bandello, MD and G. Querques, MD from the IRCCS Ospedale San Raffaele, was described.  Either standard or sub-threshold laser strategies have been tried to induce regression of distinct phenotypes of ARMD, as reticular pseudo-drusen (RPD), nascent geographic atrophy (nGA), and drusen-associated geographic atrophy (DAGA), with heterogeneous results.  The aim of the PASCAL-GA protocol was to examine if sub-threshold laser could restore the retinal pigment epithelium (RPE) function in eyes with RPD and nGA offering a protective effect against extensive GA.  The authors concluded that new-generation medical and surgical approaches, including sub-threshold laser photocoagulation, may have some success in down-staging ARMD.

In a review on "Prophylactic laser in age-related macular degeneration", Findlay and associates (2018) stated that it is now well established that photocoagulation using the traditional thermal laser results in clearance of drusen, but does not alter the risk of progression to advanced ARMD.  The interest now is in the short pulse duration lasers, delivered in a sub-threshold manner in the attempt to garner the beneficial effects of the laser without any damaging inflammatory effect.  These novel lasers aim to produce photo-stimulation that selectively targets the RPE without the accompanying collateral retinal damage.  As such, these new modalities in laser technology may provide promising treatments of ARMD through RPE-mediated mechanisms, which had remained unexplored initially with thermal lasers.  Currently, the Laser Intervention in Early Age-Related Macular Degeneration Study (LEAD), a multi-center randomized clinical trial using a nanosecond laser to examine progression of ARMD in 240 subjects, is underway.  These investigators were unaware of other large randomized clinical trials using other sub-threshold lasers, although smaller cohort studies and treatments continue.  The authors stated that clinical benefit of prophylactic laser application to treat ARMD, and which sub-groups of ARMD should be treated, will be further clarified once the results from the LEAD trial and other upcoming studies emerge in the near future.

Eng and colleagues (2019) noted that ARMD is the leading cause of irreversible blindness among the elderly in developed countries.  Sub-threshold retinal laser therapy is a new technique that targets drusen – a marker of nonexudative ARMD – without causing incidental retinal damage associated with conventional laser photocoagulation.  These researchers summarized published literature on sub-threshold retinal laser therapy as prophylactic treatment of non-exudative ARMD.  They carried out a literature search of the PubMed, Medline, and Embase databases from January 1997 to April 2018.  Studies were analyzed based upon study design, laser parameters, drusen reduction, changes in VA, and the development of CNV and/or GA.  A total of 12 studies involving 2,481 eyes treated with sub-threshold retinal laser therapy were included in this review.  Treatment led to increased drusen reduction, and studies with significant VA improvement were associated with significant drusen reduction.  There was no significant change in the risk of developing CNV or GA.  The authors concluded that sub-threshold retinal laser therapy was effective for reducing drusen and potentially improving vision in patients with non-exudative AMD.  Moreover, these investigators stated that this therapy did not show benefits in reducing development of CNV or GA.  Therefore, its long-term efficacy to prevent progression to advanced ARMD cannot yet be recommended.

In a prospective study, Kim and colleagues (2020) reported the 12-month safety and efficacy of laser photocoagulation and anti-VEGF injections for drusenoid pigment epithelial detachment (dPED).  Patients with treatment naïve bilateral intermediate ARMD, featuring dPED, with VA of less than or equal to 83 letters were enrolled.  The study group received PASCAL laser (532 nm) along the periphery of the dPED, and the fellow eye served as a control group.  To prevent complications of CNV, intravitreal anti-VEGF injections to the laser-treated eye were carried out on a 3-month interval up to 1 year.  Primary outcomes – drusen area, and PED height; and secondary outcomes – BCVA, contrast sensitivity, degree of metamorphopsia, NEI-VFQ 25, and fundus autofluorescence were analyzed.  Among 21 patients, a total of 20 patients satisfied the 12 months follow-up.  Drusen area and PED height decreased significantly in the laser group, while no significant change appeared in the control group (74.1 % versus - 3.5 %, p < 0.001; 76.6 % versus 0.1 %, p < 0.001).  Mean BCVA improved 4.6 letters in the laser group (versus 1.1 letters in the control group, p = 0.019).  As for safety, 1 study eye developed retinal pigment epithelial tear, and 1 control eye developed retinal angiomatous proliferation.  The authors concluded that low energy laser photocoagulation and anti-VEGF injection in eyes with dPED showed some improvement in VA.  dPED regressed without developing center involving geographic atrophy (GA) in the study eye; however, larger, randomized clinical trials with long-term follow-up period are needed to confirm the effect of this treatment protocol for intermediate ARMD.

The authors stated that this study had several drawbacks.  First, unlike the authors’ intention to observe the effects of laser to drusen, the anti-VEGF injections used to suppress CNV development might affect the course of drusenoid PED; however, drusenoid PED is thought to show a limited response to anti-VEGF therapy as these investigators normally encounter in clinical practice.  Therefore, the effect of anti-VEGF on drusenoid PED is expected to be minimal in this study.  Second, although being a prospective study, this was carried out short-term in a single center more to serve as a pilot study for multi-center randomized trials.  In AREDS2 subgroup study, time from drusenoid PED detection to appearance of central GA or neovascular AMD took 2.6 years and 2.0 years, respectively.  This was a 1-year follow-up study to examine the effect of laser for drusenoid PED.  Long-term extension studies up to 5 years is scheduled after the 1- and 2-year study period.  Third, if the fundus status (i.e., degree of drusenoid PED) were similar, eyes with lower VA were assigned to laser treatment.  Thus, interpretation of the direct comparison of VA between the treated and control eyes should be cautious because of the ceiling effect of eye with better vision.

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References