Can retinal microtrauma by internal limiting membrane peeling cause retinal angiomatosis proliferans?

A 32-year-old male presented with decreased vision in right eye since 1 month following trauma with plastic ball. Best-corrected visual acuity (BCVA) was 20/160 in right eye and 20/20 in left. Right eye examination revealed angle recession, choroidal rupture, and macular hole. He underwent vitrectomy, internal limiting membrane (ILM) peeling, and 14% C3F8 gas injection. After 6 weeks, BCVA was 20/30; fundus showed macular hole closure. Six months after surgery, fundus revealed retinal vascular lesions suggestive of stage I RAP-like lesions; vision was maintained. Clinical findings were confirmed on Video ICGA, FFA, and OCT. The patient was periodically reviewed and lesions were nonprogressive until last follow-up, 13 months after surgery. It seems quite probable that ILM peeling may have caused retinal microtrauma leading to the formation of RAP-like lesions. What factors lead to such an event is as yet not clearly understood. Hence, larger studies with a longer follow-up are warranted to better understand these findings.

Introduction

Retinal angiomatous proliferation (RAP) is a type of occult choroidal neovascularization with retinal neovascularization, contiguous telangiectasia, and variable retinal choroidal anastomosis. Apart from being associated with age-related macular degeneration (AMD), it has also been reported in eyes with toxoplasmosis, post-trauma, post-irradiation, vasoproliferative chorioretinal tumors, and idiopathic parafoveal telangiectasia. We report a case leading to the formation of RAP-like lesions following internal limiting membrane (ILM) peeling in an eye with a traumatic macular hole, hitherto unreported (PubMed search).

Case Report

A 32-year-old man presented with diminution of vision in the right eye since 1 month after sustaining an injury with a projectile plastic ball. Best-corrected visual acuity (BCVA) was 20/160; N18 in the right eye and 20/20; N6 in the left eye. Left eye was essentially normal. Gonioscopy of the right eye revealed angle recession involving two quadrants with increased trabecular pigmentation. Anterior segment findings were otherwise unremarkable. Fundus examination revealed a choroidal rupture [Figure 1a, arrow] in the superior parafoveal region and a full-thickness macular hole. Clinical findings were confirmed on optical coherence tomography (OCT) [Figure 1b]. The patient underwent vitrectomy with ILM peeling, fluid-air exchange, and 14% C3F8 gas injection. Prone positioning for 14 hours daily was advised for 10 days. On a follow-up 6 weeks after surgery, visual acuity improved to 20/30; N6 in the right eye. Fundus examination revealed a type 1 macular hole closure. Six months later, while the visual acuity was maintained, fundus examination revealed retinal vascular lesions within the area of ILM peeled-macula suggestive of stage I RAP-like lesion [Figure 2a, vertical arrow]. Clinical findings were confirmed on Video Indocyanine Green Angiography (ICGA) [Figure 2b], fundus fluorescein angiography (FFA) [Figure 2c], and OCT [Figure 2d]. Also, several small areas of focal retinal leakage were detected inferior and superotemporal to the fovea at the edge of ILM-peeled area suggestive of stage I RAP-like lesions. The patient was periodically reviewed, and the lesions were seen to be nonprogressive until the last follow-up, 13 months after surgery.

Figure 1

At presentation: (a) Color fundus photograph of the right eye reveals a choroidal rupture (arrow) and a full thickness macular hole. (b) Optical coherence tomography scan confirms the presence of the macular hole

Figure 2

Six months postoperative: (a) Color fundus photograph of the right eye reveals the presence of retinal angiomatosis retinae (RAP)-like lesion (vertical arrow), choroidal rupture (horizontal arrow), and a closed macular hole. (b) Indocyanine green angiography not only highlights the large RAP-like lesion (vertical arrow) but also reveals the several, small, incipient RAP-like lesions at the margin of the ILM-peeled area (arrowhead). (c) Late phase fundus fluorescein angiogram highlights both the large RAP-like lesion (vertical arrow) while confirming the presence of smaller RAP-like lesions (arrowhead) with late diffuse leakage. (d) Optical coherence tomography reveals the irregular, hyper-reflective area of choroidal rupture (horizontal arrow) and the intraretinal hyper-reflective lesion with shadowing (arrowhead) suggestive of RAP-like lesion

Discussion

Retinal angiomatous proliferation was recognized as deep retinal vascular complex in 1992[1] and was modified to include retinal choroidal anastomosis in 1995.[2] Finally, in 2001 it was conceptualized to the term RAP[3] after inclusion of retinal-retinal anastomosis. It accounts for 10–15% of exudative AMD and is usually bilateral in presentation.[3] It has a female preponderance and affects elderly patients. It was classified by Yanuzzi et al.[4] into three stages of progression. Stage I includes intraretinal neovascularization wherein capillary proliferation occurs from within deeper layers of the retina. It is associated with hemorrhages and retinal edema. The intraretinal neovascularization extends into subretinal space and there are more subretinal, intraretinal, and preretinal hemorrhages. This constitutes the stage II RAP lesions. Finally, in stage III a serous or vascularized pigment epithelial detachment occurs and retinal choroidal anastomosis is formed following which a choroidal neovascular membrane is seen. Later in 2003, Gass et al.[5] proposed that RAP lesion evolved from occult type 1 CNV and classified it into five stages. Stage 1 included occult type 1 choroidal neovascularization (CNV) with focal areas of atrophic retina. Stage 2 featured superficial hemorrhages between retinal capillaries and occult CNV. In stage 3, there was formation of chorioretinal anastomosis followed by serous PED in stage 4, while stage 5 included a disciform scar. In 2008, Freund et al.[6] and Yanuzzi et al.[7] described it as a type 3 neovascularization and hypothesized that this type of neovascularization does not necessarily arise from a CNV. Rather, it may originate from the choroid and may gain retinal access through de novo breaks in the Bruch's membrane. It thus encompasses three disease manifestations:

Focal neovascular complexes from deep retinal layers

Intraretinal neovasular extension from underlying occult CNV

de novo breaks in Bruch's membrane with neovascular infiltration into the retina

In another study by Hartnett et al.,[2] it was suggested that the retina may be responsible for some RPE disturbances with a secondary contribution from the choroidal vasculature. This results in an asymmetric two tier vascular membrane with a small plaque like retinal and a larger choroidal membrane.

In our reported case, it seems quite probable that retinal microtrauma caused by ILM peeling may have precipitated events leading to secondary retinal neovascularization akin to RAP lesion formation. The eye having sustained blunt trauma before might already have been prone to develop such lesions given that microbreaks in the RPE-Bruch's membrane complex cannot be ruled out. It is noteworthy that “multiple” (as opposed to typically single lesions) developed in an area far removed from the obvious choroidal rupture [Figure 2b and 2c] and were “nonprogressive” in nature. It is also possible that the incipient retinal neovascularization could have been missed in the early postoperative period. High-speed Video-ICGA has been considered as gold standard in confirming RAP lesions. OCT imaging shows the presence of retinal edema near to the RAP-like lesions. We did not see intraretinal hemorrhages and retinal exudation in our case, probably because of its nonprogressive nature. The RAP lesion is seen as a high reflective mass originating from within the retinal layers and extending deeper.

Treatment options include focal laser to lesions,[8] antivascular endothelial growth factor therapy,[9] PDT, and IVTA.[10] RAP lesions have very poor functional and visual prognosis, and various treatment options do not help in preventing the same. However, in our case, the patient has been kept on close follow-up without active intervention, considering the good level of visual acuity in that eye and the “nonprogressive” nature of the lesions. It is a unique case where ILM peeling in traumatic macular hole surgery has probably led to formation of RAP-like lesions. Probably, retinal imaging with higher resolution and histopathologic correlation would help understand the etiopathogenesis of such lesions better.