Focal/grid laser photocoagulation was the standard of care for treating diabetic macular edema (DME) until randomized clinical trials demonstrated superior visual outcomes with intravitreal anti-vascular endothelial growth factor (VEGF) therapy.1,2 As reported in the Early Treatment Diabetic Retinopathy Study, standard laser settings for treating clinically significant DME were a spot size of 50 μm to 100 μm, pulse duration of 0.1 second or less, and adequate power to obtain visible tissue whitening.3,4 Modified laser techniques including subthreshold micropulse laser with reduced power and smaller spot sizes have been explored5 to minimize adverse effects of thermal laser, which can include central and paracentral scotomata, color vision defects, progressive enlargement of laser scars, and occasional secondary macular neovascularization (MNV).6 We present multimodal imaging for a case of laser-induced retinal-choroidal anastomosis (RCA) masquerading as type 3 MNV.
A 64-year-old female was referred for evaluation of a mild visual decline in her right eye over 6 months. Ocular history included childhood strabismus surgery, bilateral cataract surgery, and bilateral focal/grid laser for DME performed elsewhere several years previously. Medical history included well-controlled type 2 diabetes, chronic renal failure requiring renal transplantation 3 years previously, and congestive heart failure treated with coronary artery bypass surgery and mitral valve repair 3 years earlier.
On examination, best-corrected visual acuity (BCVA) was 20/40 in each eye. Findings of nonproliferative diabetic retinopathy were noted in both eyes (Figure 1A). Findings of age-related macular degeneration (AMD), such as soft drusen or subretinal drusenoid deposits, were absent. Fundus autofluorescence showed multiple hypoautofluorescent spots consistent with prior focal/grid laser (Figure 1B). Spectral-domain optical coherence tomography (SD-OCT) (Spectralis HRA+OCT; Heidelberg Engineering, Heidelberg, Germany) of the right eye demonstrated intraretinal fluid in the temporal macula related to mild DME. At the temporal margin of the foveal pit, there was an intraretinal hyperreflective lesion that extended from the outer plexiform layer through a disrupted retinal pigment epithelium (RPE)/Bruch's membrane complex (Figures 1C–1E). Swept-source OCT angiography (SS-OCTA) (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA) showed flow signal within the intraretinal lesion extending below the deep capillary plexus into the inner choroidal slab (Figures 1F–1H). The structural details of the vascular complex were more readily seen in a three-dimensional rendering of OCT structure and OCT angiography flow signal data created using a “dense B-scan” OCTA7 (OCT2 platform; Heidelberg Engineering, Heidelberg, Germany) volume (See Supplemental Video below).
Multimodal imaging of the right eye. (A) Confocal true color fundus photograph shows findings of nonproliferative diabetic retinopathy including scattered intraretinal hemorrhages and lipid exudates temporal to the fovea. (B) Fundus autofluorescence and (C) en face structural slab from the retinal pigment epithelium (RPE) to Bruch's membrane obtained using the in-built segmentation software of the Spectralis HRA+OCT aligned to the near-infrared reflectance image both show evidence of prior focal/grid laser. (D, E) Optical coherence tomography (OCT) B-scans corresponding to the green lines in C. (D) A representative OCT B-scan from the superior macula shows discontinuity of ellipsoid and interdigitation zones at the site of prior laser. (E) Central OCT B-scan shows temporal retinal thickening and a hyperreflective intraretinal lesion extending from the outer plexiform layer through a disrupted RPE/Bruch's membrane complex. (F) A 3 mm × 3 mm color retina depth-encoded OCT angiography (OCTA) image with two veins labeled as “V” and two arteries labeled as “A.” The vascular complex is marked with a white arrowhead. The presence of vascular flow is seen as red overlay on a corresponding cross-sectional OCT B-scan (G), and the default outer retina to choriocapillaris (ORCC) slab (H) marked with a yellow arrowhead.
The patient was monitored at intervals of 2 to 3 months over a period of 3 years. Eye-tracked SD-OCT showed the intraretinal hyperreflective lesion remaining stable with minimal change in intraretinal fluid and no evidence of subretinal fluid, lipid, or hemorrhage (Figure 2). Mild DME was persistent, but BCVA was stable (20/30 to 20/40). Based on the history of prior focal/grid laser for DME, multimodal imaging findings, and the nonprogressive nature of the lesion, a diagnosis of inadvertent creation of a laser-induced RCA was made.
Follow-up images show the nonprogressive nature of the vascular complex. (B to K) Eye-tracked spectral-domain optical coherence tomography images at different time points taken through the green line in the near-infrared reflectance image (A).
An RCA can occur due to the natural course of disease in neovascular AMD,8,9 macular telangiectasis Type 2 (MacTel2),10 inflammatory disorders such as toxoplasmosis chorioretinitis and ocular histoplasmosis,11–13 pseudoxanthoma elasticum,12 and ocular trauma.14 Intentional laser-induced RCA for treating central retinal vein occlusion (CRVO) was first described by McAllister et al. to provide an alternate drainage route for retinal venous blood by rupturing both the walls of a retinal vein and Bruch's membrane.15,16 With this technique, a high-power density laser was used to create a connection between a retinal vein where the intraluminal pressure was high due to the obstruction of venous outflow and an unobstructed choroidal vein with normal pressure. Settings used included argon green laser (wavelength 514 nm), a spot size of 50 μm, pulse duration of 0.1 seconds, and power level of at least 1.5 W in order to rupture the Bruch's membrane first, followed by rupturing the retinal vein using a power level of 2.5 W to 6 W, depending on the degree of lens opacity or retinal edema. YAG laser with a setting of 3 mJ to 4 mJ was used if argon laser failed to rupture the retinal vein.17,18
Although uncommon, inadvertent rupture of Bruch's membrane can occur during focal/grid laser for DME when excessive laser energy is used with a small treatment spot size. Pigments within the macula region that absorb commonly used laser wavelengths and their respective peak absorption spectra are xanthophylls within the neurosensory retina (420 nm to 500 nm), melanin within the RPE cells and choroidal melanocytes (400 nm to 1,000 nm), and hemoglobin (450 nm to 550 nm),19 so the laser treatment can produce focal disruption of both the RPE/Bruch's membrane complex and walls of small retinal vessels resulting in an inadvertent creation of a RCA.
RCA is considered a late-stage occurrence in eyes with neovascular AMD and type 3 MNV.8,20–22 Although treatment outcomes for eyes with type 3 MNV have improved since the advent of intravitreal anti-VEGF therapy, continuous treatment may be required and progressive macular atrophy may ultimately lead to loss of central vision.23,24 Our patient lacked clinical findings of AMD and her age of 64 years would be unusually young for a patient presenting with type 3 MNV due to AMD. There were no findings of macular telangiectasia type 2, inflammatory chorioretinitis, or pseudoxanthoma elasticum. The history of prior focal/grid laser for DME and the nonprogressive nature of the lesion over a multi-year follow-up supported the diagnosis of laser-induced RCA.
Of note, in 1980, Slusher et al. described fluorescence angiography manifestations in a case of “choroidoretinal vascular anastomoses” associated with hypertensive and diabetic retinopathy.12 Grid laser treatment had been performed, but an abnormal large anastomotic vein appearing to drain into the choroid had been noted prior to laser treatment. Due to the lack of high-quality multimodal imaging, the role of grid laser in forming this RCA cannot be established.
To the best of our knowledge, this is the first report of a focal/grid laser-induced RCA masquerading as type 3 MNV. Our case reinforces the need to choose appropriate laser settings when performing macular treatments in order minimize collateral damage to surrounding retinal structures.
- Schmidt-Erfurth U, Garcia-Arumi J, Bandello F, et al. Guidelines for the Management of Diabetic Macular Edema by the European Society of Retina Specialists (EURETINA). Ophthalmologica. 2017;237(4):185–222. doi:10.1159/000458539 [CrossRef] PMID:28423385
- Blindbaek SL, Peto T, Grauslund J. How do we evaluate the role of focal/grid photocoagulation in the treatment of diabetic macular edema?Acta Ophthalmol. 2019;97(4):339–346. doi:10.1111/aos.13997 [CrossRef] PMID:30575304
- Early Treatment Diabetic Retinopathy Study Research Group. Treatment techniques and clinical guidelines for photocoagulation of diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 2. Ophthalmology. 1987;94(7):761–774. doi:10.1016/S0161-6420(87)33527-4 [CrossRef] PMID:3658348
- Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study report number 1. Early Treatment Diabetic Retinopathy Study research group. Arch Ophthalmol. 1985;103(12):1796–1806. doi:10.1001/archopht.1985.01050120030015 [CrossRef] PMID:2866759
- Vujosevic S, Martini F, Longhin E, Convento E, Cavarzeran F, Midena E. Subthreshold Micropulse Yellow Laser Versus Subthreshold Micropulse Infrared Laser in Center-Involving Diabetic Macular Edema: Morphologic and Functional Safety. Retina. 2015;35(8):1594–1603. doi:10.1097/IAE.0000000000000521 [CrossRef] PMID:25719988
- Luttrull JK, Dorin G. Subthreshold diode micropulse laser photocoagulation (SDM) as invisible retinal phototherapy for diabetic macular edema: a review. Curr Diabetes Rev. 2012;8(4):274–284. doi:10.2174/157339912800840523 [CrossRef] PMID:22587512
- Freund KB, Gattoussi S, Leong BCS. Dense B-Scan Optical Coherence Tomography Angiography. Am J Ophthalmol. 2018;190:78–88. doi:10.1016/j.ajo.2018.03.029 [CrossRef] PMID:29601820
- Yannuzzi LA, Negrão S, Iida T, et al. Retinal angiomatous proliferation in age-related macular degeneration. Retina. 2001;21(5):416–434. doi:10.1097/00006982-200110000-00003 [CrossRef] PMID:11642370
- Slakter JS, Yannuzzi LA, Schneider U, et al. Retinal choroidal anastomoses and occult choroidal neovascularization in age-related macular degeneration. Ophthalmology. 2000;107(4):742–753. doi:10.1016/S0161-6420(00)00009-9 [CrossRef] PMID:10768338
- Spaide RF, Yannuzzi LA, Maloca PM. Retinal-Choroidal Anastomosis in Macular Telangiectasia Type 2. Retina. 2018;38(10):1920–1929. doi:10.1097/IAE.0000000000002289 [CrossRef] PMID:30095711
- Doft BH. Choroidoretinal vascular anastomosis. Arch Ophthalmol. 1983;101(7):1053–1054. doi:10.1001/archopht.1983.01040020055009 [CrossRef] PMID:6870628
- Slusher MM, Tyler ME. Choroidoretinal vascular anastomoses. Am J Ophthalmol. 1980;90(2):217–222. doi:10.1016/S0002-9394(14)74856-1 [CrossRef] PMID:7425032
- Tabbara KF. Disruption of the choroidoretinal interface by toxoplasma. Eye (Lond). 1990;4(Pt 2):366–373. doi:10.1038/eye.1990.49 [CrossRef] PMID:2199243
- Archer DB, Canavan YM. Contusional eye injuries: retinal and choroidal lesions. Aust J Ophthalmol. 1983;11(4):251–264. doi:10.1111/j.1442-9071.1983.tb01090.x [CrossRef] PMID:6667198
- McAllister IL, Yu DY, Vijayasekaran S, Barry C, Constable I. Induced chorioretinal venous anastomosis in experimental retinal branch vein occlusion. Br J Ophthalmol. 1992;76(10):615–620. doi:10.1136/bjo.76.10.615 [CrossRef] PMID:1420044
- McAllister IL, Constable IJ. Laser-induced chorioretinal venous anastomosis for treatment of nonischemic central retinal vein occlusion. Arch Ophthalmol. 1995;113(4):456–462. doi:10.1001/archopht.1995.01100040072030 [CrossRef] PMID:7710396
- McAllister IL, Vijayasekaran S, Xia W, Yu DY. Evaluation of the ability of a photocoagulator to rupture the retinal vein and Bruch's membrane for potential vein bypass in retinal vein occlusion. Ophthalmic Surg Lasers Imaging Retina. 2013;44(3):268–273. doi:10.3928/23258160-20130503-10 [CrossRef] PMID:23676229
- McAllister IL, Vijayasekaran S, Yu DY, Constable IJ. Chorioretinal venous anastomoses: effect of different laser methods and energy in human eyes without vein occlusion. Graefes Arch Clin Exp Ophthalmol. 1998;236(3):174–181. doi:10.1007/s004170050060 [CrossRef] PMID:9541819
- Yadav NK, Jayadev C, Rajendran A, Nagpal M. Recent developments in retinal lasers and delivery systems. Indian J Ophthalmol. 2014;62(1):50–54. doi:10.4103/0301-4738.126179 [CrossRef] PMID:24492501
- Freund KB, Ho IV, Barbazetto IA, et al. Type 3 neovascularization: the expanded spectrum of retinal angiomatous proliferation. Retina. 2008;28(2):201–211. doi:10.1097/IAE.0b013e3181669504 [CrossRef] PMID:18301024
- Yannuzzi LA, Freund KB, Takahashi BS. Review of retinal angiomatous proliferation or type 3 neovascularization. Retina. 2008;28(3):375–384. doi:10.1097/IAE.0b013e3181619c55 [CrossRef] PMID:18327130
- Freund KB, Zweifel SA, Engelbert M. Do we need a new classification for choroidal neovascularization in age-related macular degeneration?Retina. 2010;30(9):1333–1349. doi:10.1097/IAE.0b013e3181e7976b [CrossRef] PMID:20924258
- Li J, Xu J, Chen Y, Zhang J, Cao Y, Lu P. Efficacy Comparison of Intravitreal Anti-VEGF Therapy for Three Subtypes of Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis. J Ophthalmol. 2018;2018:1425707. doi:10.1155/2018/1425707 [CrossRef] PMID:30425852
- Kim JH, Chang YS, Kim JW, Kim CG, Lee DW. Early Recurrent Hemorrhage in Submacular Hemorrhage Secondary to Type 3 Neovascularization or Retinal Angiomatous Proliferation: Incidence and Influence on Visual Prognosis. Semin Ophthalmol. 2018;33(6):820–828. doi:10.1080/08820538.2018.1511814 [CrossRef] PMID:30136868