Variable response of sub-retinal hyper-reflective membranes to anti-vascular endothelial growth factor treatment in bilateral neo-vascular age-related macular degeneration: A case report

Debdulal Chakraborty; Soumen Mondal; Subhendu Boral; Asmita Saha

doi:10.4103/ijo.IJO_2034_22

CASE REPORT

Year : 2023 | Volume : 3 | Issue : 2 | Page : 441-444

Variable response of sub-retinal hyper-reflective membranes to anti-vascular endothelial growth factor treatment in bilateral neo-vascular age-related macular degeneration: A case report

Debdulal Chakraborty, Soumen Mondal, Subhendu Boral, Asmita Saha
Department of Vitreoretina Services, Disha Eye Hospitals, Kolkata, West Bengal, India

Date of Submission	16-Aug-2022
Date of Acceptance	31-Jan-2023
Date of Web Publication	28-Apr-2023

Correspondence Address:
Debdulal Chakraborty
Department of Vitreoretina Services, Disha Eye Hospitals, 88 Ghosh Para Road, Barrackpore, Kolkata - 700 120, West Bengal
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijo.IJO_2034_22

Abstract

Sub-retinal hyper-reflective material (SHRM) is an important spectral-domain optical coherence tomography biomarker in neo-vascular age-related macular degeneration (nAMD). The exact nature of SHRM is not known, but it may contain fluid, fibrin, blood, neo-vascular tissue, and so on. Although nAMD with avascular SHRM usually resolves with anti-vascular endothelial growth factor and is known to have better visual prognosis, those with vascular SHRM have significantly poor final vision. We present a unique case of nAMD with an avascular SHRM in the right eye and a vascular SHRM in the left eye and how the two eyes behaved with treatment over a period of 12 months.

Keywords: Anti-vascular endothelial growth factor treatment, neo-vascular AMD, sub-retinal hyper-reflective material (SHRM)

How to cite this article:
Chakraborty D, Mondal S, Boral S, Saha A. Variable response of sub-retinal hyper-reflective membranes to anti-vascular endothelial growth factor treatment in bilateral neo-vascular age-related macular degeneration: A case report. Indian J Ophthalmol Case Rep 2023;3:441-4

How to cite this URL:
Chakraborty D, Mondal S, Boral S, Saha A. Variable response of sub-retinal hyper-reflective membranes to anti-vascular endothelial growth factor treatment in bilateral neo-vascular age-related macular degeneration: A case report. Indian J Ophthalmol Case Rep [serial online] 2023 [cited 2023 Jun 6];3:441-4. Available from: https://www.ijoreports.in/text.asp?2023/3/2/441/374925

Sub-retinal hyper-reflective material (SHRM) is an important spectral-domain optical coherence tomography (SD-OCT) biomarker and is present in 77% of eyes with neo-vascular age-related macular degeneration (nAMD).^[1] Although the exact nature of SHRM is not known, authors suggest that SHRM could contain fluid, fibrin, blood, neo-vascular tissue, or scar.^[2],[3] Eyes with SHRM have poor vision due to either the toxic effect on photo-receptors or the barrier effect, impeding nutrient and metabolite exchange.^[1] Location, shape and size of SHRM, reflectivity, borders, vascularity, and separation from the outer retina are related to prognosis.^[4] Avascular SHRM usually resolves with anti-vascular endothelial growth factor (anti-VEGF) and has better visual prognosis.^[5] Vascular SHRM, which constitutes almost half of all SHRM, has significantly poor final vision.^[4],[6]

We present a unique case of nAMD with an avascular SHRM in the right eye (OD) and a vascular SHRM in the left eye (OS). Written informed consent was obtained from the patient, and necessary steps were taken to prevent disclosure of identity. This case report was provided a waiver by the Institutional Review Board.

Case Report

A 64-year-old lady presented with decreased vision (20/60) in OD for 7 days. Anterior segment examination was normal. Fundus examination revealed pigment epithelial detachment (PED) surrounded by sub-retinal hemorrhage (SRH) and yellowish sub-retinal material [Figure 1]a. The auto-fluorescence (AF) image did not reveal any hyper-AF [Figure 1]b. Multi-lobular PED (ML-PED), SHRM, and sub-retinal fluid (SRF) were noted on SD-OCT [Figure 1]c. Enface OCT (Ef-OCT) revealed ML-PED, along with macular neo-vascularization (MNV) [Figure 2]a. OCT angiography (OCTA) did not show any high flow areas within the SHRM [Figure 2]b. Following three loading doses of intravitreal aflibercept (IVI-AFL), VA improved to 20/25 with decreased SHRM and SRH [Figure 1]d and [Figure 1]e. There was corresponding resolution of SHRM and regression of ML-PED [Figure 1]f. SD-OCT revealed regression of SHRM and significant reduction of PED height [Figure 2]b. After 3 IVI-AFL, Ef-OCT shows regression of PED and mature MNV vessels [Figure 2]c. OCTA shows no flow signals within the SHRM [Figure 2]d. The fourth IVI-AFL was injected at 8 weeks, followed by 2-week extensions for the fifth and sixth. The final VA at 12 months was 20/25. Optos colour image, AF and SD OCT at 12 months is depicted in [Figure 1]g, [Figure 1]h, [Figure 1]i. At 12 months Ef OCT shows few mature vessels [Figure 2]e Corresponding OCTA shows no flow [Figure 2]f.

Figure 1: Baseline optos (OI) and auto-fluorescence (AF) of the right eye (OD) showing sub-retinal hem (SRH) (green asterix) with sub-retinal yellow lesion (SHRM, yellow asterix) (a), noted as halo with no hyper-AF (b). Corresponding SDOCT shows SHRM (red asterix) with adjacent subretinal fluid (yellow arrowhead) and multi-lobular (ML) PED (green arrowhead) (c). OI and AF after loading dose of aflibercept (IVI-AFL) showing minimal SRH (green arrowhead) and SHRM resolution (d and e). Corresponding SD-OCT shows resolution of SHRM and regression of ML PED (green arrowhead). (f) At 12 months, OI and AF show scarring temporal to fovea (white arrowhead). (g and h) SD-OCT shows significant normalization of retinal contour (i)

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Figure 2: Baseline enface OCT (Ef-OCT) of OD showing multi-lobular PED (yellow asterix) and macular neo-vascularization (MNV) (a) and corresponding baseline cross-sectional OCT with angiographic overlay (OCTA) (red pixels) showing no flow signals within the SHRM (green arrowhead) (b). After 3 IVI-AFL, Ef-OCT shows regression of PED (yellow asterix) and mature MNV vessels (yellow arrowhead). (c) OCTA after loading dose showing no flow signals within the SHRM (d). At 12 months, Ef-OCT shows few mature vessels (e) and OCTA with no flow signals within the SHRM (f)

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In OS, the baseline VA was 20/80. Slit-lamp examination revealed early sub-capsular cataract. Fundus examination revealed minimal SRH and yellowish sub-retinal material [Figure 3]a, which lacked hyper-AF [Figure 3]b. A foveal SHRM with overlying SRF was noted on SD-OCT [Figure 3]c. Ef-OCT revealed a neo-vascular network [Figure 4]a, and OCTA revealed high flow areas within the SHRM [Figure 4]b, suggestive of vascularity [Figure 3]g and [Figure 3]i. Following three loading doses of IVI-AFL, VA remained at 20/80. Fundus examination revealed persistence of the yellow sub-retinal lesion but no SRH [Figure 3]d and [Figure 3]e. SD-OCT at 3 months showed a persistent high-reflective SHRM with reduction of SRF [Figure 3]f. Ef-OCT showed mature vessels [Figure 4]c, but OCTA lacked high flow signals [Figure 4]d within the SHRM. The fourth IVI-AFL was injected 8 weeks after loading dose, followed by re-injection 8 weeks later. SRF resolved at 28 weeks from baseline. IVI-AFL was continued thereafter with 2-week extensions. The vision was 20/100 at final follow-up of 12 months. The fundus showed sub-retinal yellow lesion [Figure 3]g and [Figure 3]h with persistence of a well-defined high-reflective SHRM on SD-OCT [Figure 3]i, mature vessels on Ef-OCT [Figure 4]e, and no high flow areas on OCTA [Figure 4]f.

Figure 3: At baseline, OI of left eye (OS) showing sub-retinal hem (green arrowhead) a sub-retinal yellow lesion (SHRM, yellow arrowhead) (a) and auto-fluorescence (AF) image with no hyper-AF (b). Corresponding SD-OCT showing intra-retinal fluid (yellow arrowhead), sub-retinal fluid (SRF, yellow asterix), hyper-reflective SHRM (red asterix), and multi-lobular PED (green arrowhead) (c). After three loading doses of IVI-AFL, OI and AF of OS show persistence of the yellow sub-retinal lesion but no SRH (d and e) and SD-OCT showing a decrease of SRF (yellow asterix) but persistence of SHRM (red asterix) (f). At 1 year, OI and AF show sub-retinal yellow lesion which does not show any hyper-AF (g and h). Corresponding SD-OCT showing persistence of a well-defined high-reflective SHRM with low-reflective intra-lesional areas (i)

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Figure 4: Baseline Ef-OCT of left eye (OS) showing the vascular network within SHRM (a), with corresponding OCTA showing high flow areas suggestive of vascular SHRM. (b) At 3 months and 1 year, Ef-OCT shows mature vessels within SHRM (c and e), while corresponding OCTA shows the absence of high flow areas within the SHRM (d and f)

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Discussion

The purpose of this case report was to demonstrate response to anti-VEGF therapy over 12 months in a patient of nAMD with bilateral SHRM. The avascular SHRM in OD showed resolution with improvement of vision, whereas the vascular SHRM in OS showed persistence with decreased vascularity and a mild decrease of vision.

The role of SHRM as a biomarker in nAMD is important as it offers strong correlation with visual acuity.^[1],[4] Advances in in vivo imaging, particularly SD-OCT, have improved the detection and characterization of SHRM.^[7] SHRM can be differentiated based on the shape, location, reflectivity, borders, and vascularity.^[7] Depending on shape of the SHRM, it can be categorized as tall, flat, or dysmorphic. Tall SHRMs are described as a dome-shaped lesion within the foveal center having a maximum height of at least 120 microns, a flat-thin disc-shaped lesion less than 80 microns high, and a dysmorphic lesion, with an irregular shape. Based on the location, SHRM may be foveal or extra-foveal. Based on reflectivity, SHRMs have been graded as 1) iso-dense with the outer plexiform layer (OPL), 2) iso-dense with the retinal nerve fiber layer (RNFL), or 3) reflectivity in between those of OPL and RNFL. Border demarcation of SHRM is possible with SD-OCT, and it is described as well-defined if more than 75% of the SHRM border is clearly distinguishable, mixed if 25% to 75% of borders are traceable, and poorly defined if less than 25% of borders are clearly identified. Intra-lesional vascularity of SHRM enables the differentiation into vascular and avascular varieties, the diagnosis of which is possible using OCTA.^[7],[8]

In the current patient, SD-OCT detected the SHRM and OCTA was able to differentiate between avascular SHRM in OD and the vascular one in OS, respectively. In OD, the avascular SHRM showed resolution following the loading dose of IVI-AFL and also progressive normalization of the retinal contour demonstrated by the SD-OCT. In OS, the vascular SHRM became more organized with higher internal reflectivity and well-defined borders. The neo-vascular network and its maturity with treatment were well demonstrated by the OCTA. Disappearance of the SHRM following treatment with anti-VEGF has been associated with good visual prognosis, but a decreased lesion height with increasing reflectivity occurs because of increasing consolidation, reflecting progressive fibrotic scar formation, associated with poor visual acuity.^[1],[4],[8] The rapid decrease in SHRM thickness is caused by reduction in the fluid component of SHRM induced by anti-VEGF therapy. AntiVEGF can block the angiogenesis, but it is less effective at decreasing the size of the already formed neo-vascular complex, leaving behind the fibrotic scar component that does not resolve.^[8],[9]

In eyes with nAMD, vascular SHRM remains after treatment and has lower response to anti-VEGF therapy.^[1],[4],[8] The loading dose of anti-VEGF therapy has been noted to significantly decrease the dimension and height, especially in avascular SHRM, primarily because of reduced vascular fluid leakage, leading to decreased capillary endothelial permeability.^[1],[4],[10] This was noted in the right eye of the patient. However, in eyes with vascular SHRM, there may be an increased fibrotic component, rendering anti-VEGF therapy less effective in reducing the SHRM thickness,^[8],[9],[10] as was noted in the left eye of the current patient.

Although the location of the SHRM was sub-foveal in both eyes of the patient, the avascular nature of SHRM in OD leads to resolution with anti-VEGF. In OS, maturation of the neo-vascular complexes leads toward a hyper-reflective organized fibrotic lesion with well-defined borders and poor visual prognosis.

Conclusion

To conclude, characterization of SHRM may help in providing better treatment, adequate disease control, and minimized recurrence and neuro-sensory damage, thereby helping improve vision in eyes with nAMD.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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