The progress of the study of lipid globules in the retina and choroid_Chinese Journal of Ocular Fundus Diseases

Authors：

Li Pingping ¹ , Li Lu ² ,  Wu Jianhua ¹

1. Aier Eye Hospital of Wuhan University, Wuhan 430000, China;
2. Eye Center, Renmin Hospital of Wuhan University, Wuhan 430000, China;

Corresponding author：

Wu Jianhua, Email: wjheye@163.com

Keywords：

Lipid globules; Age-related macular degeneration; Retina; Choroidal; Tomography, optical coherence; Review

DOI：

10.3760/cma.j.cn511434-20230911-00380

Video：

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Lipid globules in retina and choroid are new definitions based on pathology and high-resolution optical coherence tomography (OCT). OCT examination shows that the lipid globules are low reflective circular cavities in the choroid and retina, without strong reflective boundaries around them, followed by a characteristic superreflective tail. It occurs in healthy human eyes and in age-related macular degeneration characterized by retinal pigment epithelium (RPE) atrophy. Its characteristic superreflective tail is the key to distinguishing it from other diseases. At present, the understanding of lipid globules is still in the initial stage. Although lipid globules can be observed in healthy human eyes, a certain prevalence rate indicates that they are associated with choroidal hypoperfusion and RPE atrophy. In the future, larger randomized controlled trials and longer follow-up time are needed to explore its pathogenesis, pathological characteristics and treatment prognosis.

Citation： Li Pingping, Li Lu, Wu Jianhua. The progress of the study of lipid globules in the retina and choroid. Chinese Journal of Ocular Fundus Diseases, 2024, 40(4): 324-328. doi: 10.3760/cma.j.cn511434-20230911-00380 Copy

1.	Friedman E, Smith TR. Clinical and pathological study of choroidal lipid globules[J]. Arch Ophthalmol, 1966, 75(3): 334-336. DOI: 10.1001/archopht.1966.00970050336006.
2.	Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model[J]. Retina, 2011, 31(8): 1609-1619. DOI: 10.1097/IAE.0b013e3182247535.
3.	Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography[J]. Am J Ophthalmol, 2008, 146(4): 496-500. DOI: 10.1016/j.ajo.2008.05.032.
4.	Dolz-Marco R, Glover JP, Gal-Or O, et al. Choroidal and sub-retinal pigment epithelium caverns: multimodal imaging and correspondence with friedman lipid globules[J]. Ophthalmology, 2018, 125(8): 1287-1301. DOI: 10.1016/j.ophtha.2018.02.036.
5.	Bonnet C, Querques G, Zerbib J, et al. Hyperreflective pyramidal structures on optical coherence tomography in geographic atrophy areas[J]. Retina, 2014, 34(8): 1524-1530. DOI: 10.1097/IAE.0000000000000165.
6.	Joyal JS, Sun Y, Gantner ML, et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1[J]. Nat Med, 2016, 22(4): 439-445. DOI: 10.1038/nm.4059.
7.	Young SG, Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis[J]. Genes Dev, 2013, 27(5): 459-484. DOI: 10.1101/gad.209296.112.
8.	Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain[J]. Mol Neurobiol, 2011, 44(2): 203-215. DOI: 10.1007/s12035-010-8162-0.
9.	Querques G, Costanzo E, Miere A, et al. Choroidal caverns: a novel optical coherence tomography finding in geographic atrophy[J]. Invest Ophthalmol Vis Sci, 2016, 57(6): 2578-2582. DOI: 10.1167/iovs.16-19083.
10.	Mullins RF, Johnson MN, Faidley EA, et al. Choriocapillaris vascular dropout related to density of drusen in human eyes with early age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(3): 1606-1612. DOI: 10.1167/iovs.10-6476.
11.	Yabushita H, Bouma BE, Houser SL, et al. Characterization of human atherosclerosis by optical coherence tomography[J]. Circulation, 2002, 106(13): 1640-1645. DOI: 10.1161/01.cir.0000029927.92825.f6.
12.	Liu L, Gardecki JA, Nadkarni SK, et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography[J]. Nat Med, 2011, 17(8): 1010-1014. DOI: 10.1038/nm.2409.
13.	Errera MH, Liyanage SE, Elgohary M, et al. Using spectral-domain optical coherence tomography imaging to identify the presence of retinal silicone oil emulsification after silicone oil tamponade[J]. Retina, 2013, 33(8): 1567-1573. DOI: 10.1097/IAE.0b013e318287d9ea.
14.	Pang CE, Messinger JD, Zanzottera EC, et al. The onion sign in neovascular age-related macular degeneration represents cholesterol crystals[J]. Ophthalmology, 2015, 122(11): 2316-2326. DOI: 10.1016/j.ophtha.2015.07.008.
15.	Mrejen S, Sato T, Fisher Y, et al. Intraretinal and intra-optic nerve head silicone oil vacuoles using adaptive optics[J]. Ophthalmic Surg Lasers Imaging Retina, 2014, 45(1): 71-73. DOI: 10.3928/23258160-20131220-11.
16.	Schmitt JM, Kumar G. Turbulent nature of refractive-index variations in biological tissue[J]. Opt Lett, 1996, 21(16): 1310-1312. DOI: 10.1364/ol.21.001310.
17.	Marmorstein AD, Marmorstein LY, Sakaguchi H, et al. Spectral profiling of autofluorescence associated with lipofuscin, Bruch's membrane, and sub-RPE deposits in normal and AMD eyes[J]. Invest Ophthalmol Vis Sci, 2002, 43(7): 2435-2441.
18.	Ohno-Matsui K, Akiba M, Moriyama M, et al. Intrachoroidal cavitation in macular area of eyes with pathologic myopia[J]. Am J Ophthalmol, 2012, 154(2): 382-393. DOI: 10.1016/j.ajo.2012.02.010.
19.	Schoenberger SD, Agarwal A. Intrachoroidal cavitation in North Carolina macular dystrophy[J]. JAMA Ophthalmol, 2013, 131(8): 1073-1076. DOI: 10.1001/jamaophthalmol.2013.1598.
20.	Dolz-Marco R, Gal-Or O, Freund KB. Choroidal thickness influences near-infrared reflectance intensity in eyes with geographic atrophy due to age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2016, 57(14): 6440-6446. DOI: 10.1167/iovs.16-20265.
21.	Miguel AI, Henriques F, Azevedo LF, et al. Systematic review of Purtscher's and Purtscher-like retinopathies[J]. Eye (Lond), 2013, 27(1): 1-13. DOI: 10.1038/eye.2012.222.
22.	Agrawal A, McKibbin MA. Purtscher's and Purtscher-like retinopathies: a review[J]. Surv Ophthalmol, 2006, 51(2): 129-136. DOI: 10.1016/j.survophthal.2005.12.003.
23.	Ferris FL, Davis MD, Clemons TE, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18[J]. Arch Ophthalmol, 2005, 123(11): 1570-1574. DOI: 10.1001/archopht.123.11.1570.
24.	Lee H, Ji B, Chung H, et al. Correlation between optical coherence tomographic hyperreflective foci and visual outcomes after anti-VEGF treatment in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy[J]. Retina, 2016, 36(3): 465-475. DOI: 10.1097/iae.0000000000000645.
25.	Coscas G, De Benedetto U, Coscas F, et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration[J]. Ophthalmologica, 2013, 229(1): 32-37. DOI: 10.1159/000342159.
26.	Xia Y, Feng N, Hua R. "Choroidal caverns" spectrum lesions[J]. Eye (Lond), 2021, 35(5): 1508-1512. DOI: 10.1038/s41433-020-1074-y.
27.	Sakurada Y, Leong BCS, Parikh R, et al. Association between choroidal caverns and choroidal vascular hyperpermeability in eyes with pachychoroid diseases[J]. Retina, 2018, 38(10): 1977-1983. DOI: 10.1097/IAE.0000000000002294.
28.	Guo X, Zhou Y, Gu C, et al. Characteristics and classification of choroidal caverns in patients with various retinal and chorioretinal diseases[J/OL]. J Clin Med, 2022, 11(23): 6994[2022-11-26]. https://pubmed.ncbi.nlm.nih.gov/36498569/. DOI: 10.3390/jcm11236994.
29.	Biesemeier A, Taubitz T, Julien S, et al. Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration[J]. Neurobiol Aging, 2014, 35(11): 2562-2573. DOI: 10.1016/j.neurobiolaging.2014.05.003.
30.	Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from classification of atrophy consensus meetings[J] Ophthalmology, 2017, 124(4): 464-478. DOI: 10.1016/j.ophtha.2016.12.002.
31.	Ferris FL 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration[J]. Ophthalmology, 2013, 120(4): 844-851. DOI: 10.1016/j.ophtha.2012.10.036.
32.	Wong CW, Yanagi Y, Lee WK, et al. Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians[J]. Prog Retin Eye Res, 2016, 53: 107-139. DOI: 10.1016/j.preteyeres.2016.04.002.
33.	Srivastava SK, Csaky KG. Identification of well-defined intrachoroidal neovascularization by high-speed indocyanine green angiography[J]. Retina, 2003, 23(5): 712-714. DOI: 10.1097/00006982-200310000-00019.
34.	Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group[J]. Ophthalmology, 2020, 127(5): 616-636. DOI: 10.1016/j.ophtha.2019.11.004.
35.	Fragiotta S, Parravano M, Costanzo E, et al. Subretinal lipid globules an early biomarker of macular neovascularization in eyes with intermediate age-related macular degeneration[J/OL]. Retina, 2023, 2023: E1 (2013-02-07)[2023-09-11]. https://pubmed.ncbi.nlm.nih.gov/36763979/. DOI: 10.1097/IAE.0000000000003760. [published online ahead of print].
36.	Kohno H, Sakai T, Saito S, et al. Treatment of experimental autoimmune uveoretinitis with atorvastatin and lovastatin[J]. Exp Eye Res, 2007, 84(3): 569-576. DOI: 10.1016/j.exer.2006.11.011.
37.	Diaz-Llopis M, Gallego-Pinazo R, Garcia-Delpech S, et al. General principles for the treatment of non-infectious uveitis[J]. Inflamm Allergy Drug Targets, 2009, 8(4): 260-265. DOI: 10.2174/187152809789352203.
38.	Jabs DA, Nussenblatt RB, Rosenbaum JT, et al. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop[J]. Am J Ophthalmol, 2005, 140(3): 509-516. DOI: 10.1016/j.ajo.2005.03.057.
39.	Begaj T, Yuan A, Lains I, et al. Presence of choroidal caverns in patients with posterior and panuveitis[J/OL]. Biomedicines, 2023, 11(5): 1268[2023-04-25]. https://pubmed.ncbi.nlm.nih.gov/37238939/. DOI: 10.3390/biomedicines11051268.

1. Friedman E, Smith TR. Clinical and pathological study of choroidal lipid globules[J]. Arch Ophthalmol, 1966, 75(3): 334-336. DOI: 10.1001/archopht.1966.00970050336006.
2. Spaide RF, Curcio CA. Anatomical correlates to the bands seen in the outer retina by optical coherence tomography: literature review and model[J]. Retina, 2011, 31(8): 1609-1619. DOI: 10.1097/IAE.0b013e3182247535.
3. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography[J]. Am J Ophthalmol, 2008, 146(4): 496-500. DOI: 10.1016/j.ajo.2008.05.032.
4. Dolz-Marco R, Glover JP, Gal-Or O, et al. Choroidal and sub-retinal pigment epithelium caverns: multimodal imaging and correspondence with friedman lipid globules[J]. Ophthalmology, 2018, 125(8): 1287-1301. DOI: 10.1016/j.ophtha.2018.02.036.
5. Bonnet C, Querques G, Zerbib J, et al. Hyperreflective pyramidal structures on optical coherence tomography in geographic atrophy areas[J]. Retina, 2014, 34(8): 1524-1530. DOI: 10.1097/IAE.0000000000000165.
6. Joyal JS, Sun Y, Gantner ML, et al. Retinal lipid and glucose metabolism dictates angiogenesis through the lipid sensor Ffar1[J]. Nat Med, 2016, 22(4): 439-445. DOI: 10.1038/nm.4059.
7. Young SG, Zechner R. Biochemistry and pathophysiology of intravascular and intracellular lipolysis[J]. Genes Dev, 2013, 27(5): 459-484. DOI: 10.1101/gad.209296.112.
8. Simopoulos AP. Evolutionary aspects of diet: the omega-6/omega-3 ratio and the brain[J]. Mol Neurobiol, 2011, 44(2): 203-215. DOI: 10.1007/s12035-010-8162-0.
9. Querques G, Costanzo E, Miere A, et al. Choroidal caverns: a novel optical coherence tomography finding in geographic atrophy[J]. Invest Ophthalmol Vis Sci, 2016, 57(6): 2578-2582. DOI: 10.1167/iovs.16-19083.
10. Mullins RF, Johnson MN, Faidley EA, et al. Choriocapillaris vascular dropout related to density of drusen in human eyes with early age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2011, 52(3): 1606-1612. DOI: 10.1167/iovs.10-6476.
11. Yabushita H, Bouma BE, Houser SL, et al. Characterization of human atherosclerosis by optical coherence tomography[J]. Circulation, 2002, 106(13): 1640-1645. DOI: 10.1161/01.cir.0000029927.92825.f6.
12. Liu L, Gardecki JA, Nadkarni SK, et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography[J]. Nat Med, 2011, 17(8): 1010-1014. DOI: 10.1038/nm.2409.
13. Errera MH, Liyanage SE, Elgohary M, et al. Using spectral-domain optical coherence tomography imaging to identify the presence of retinal silicone oil emulsification after silicone oil tamponade[J]. Retina, 2013, 33(8): 1567-1573. DOI: 10.1097/IAE.0b013e318287d9ea.
14. Pang CE, Messinger JD, Zanzottera EC, et al. The onion sign in neovascular age-related macular degeneration represents cholesterol crystals[J]. Ophthalmology, 2015, 122(11): 2316-2326. DOI: 10.1016/j.ophtha.2015.07.008.
15. Mrejen S, Sato T, Fisher Y, et al. Intraretinal and intra-optic nerve head silicone oil vacuoles using adaptive optics[J]. Ophthalmic Surg Lasers Imaging Retina, 2014, 45(1): 71-73. DOI: 10.3928/23258160-20131220-11.
16. Schmitt JM, Kumar G. Turbulent nature of refractive-index variations in biological tissue[J]. Opt Lett, 1996, 21(16): 1310-1312. DOI: 10.1364/ol.21.001310.
17. Marmorstein AD, Marmorstein LY, Sakaguchi H, et al. Spectral profiling of autofluorescence associated with lipofuscin, Bruch's membrane, and sub-RPE deposits in normal and AMD eyes[J]. Invest Ophthalmol Vis Sci, 2002, 43(7): 2435-2441.
18. Ohno-Matsui K, Akiba M, Moriyama M, et al. Intrachoroidal cavitation in macular area of eyes with pathologic myopia[J]. Am J Ophthalmol, 2012, 154(2): 382-393. DOI: 10.1016/j.ajo.2012.02.010.
19. Schoenberger SD, Agarwal A. Intrachoroidal cavitation in North Carolina macular dystrophy[J]. JAMA Ophthalmol, 2013, 131(8): 1073-1076. DOI: 10.1001/jamaophthalmol.2013.1598.
20. Dolz-Marco R, Gal-Or O, Freund KB. Choroidal thickness influences near-infrared reflectance intensity in eyes with geographic atrophy due to age-related macular degeneration[J]. Invest Ophthalmol Vis Sci, 2016, 57(14): 6440-6446. DOI: 10.1167/iovs.16-20265.
21. Miguel AI, Henriques F, Azevedo LF, et al. Systematic review of Purtscher's and Purtscher-like retinopathies[J]. Eye (Lond), 2013, 27(1): 1-13. DOI: 10.1038/eye.2012.222.
22. Agrawal A, McKibbin MA. Purtscher's and Purtscher-like retinopathies: a review[J]. Surv Ophthalmol, 2006, 51(2): 129-136. DOI: 10.1016/j.survophthal.2005.12.003.
23. Ferris FL, Davis MD, Clemons TE, et al. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18[J]. Arch Ophthalmol, 2005, 123(11): 1570-1574. DOI: 10.1001/archopht.123.11.1570.
24. Lee H, Ji B, Chung H, et al. Correlation between optical coherence tomographic hyperreflective foci and visual outcomes after anti-VEGF treatment in neovascular age-related macular degeneration and polypoidal choroidal vasculopathy[J]. Retina, 2016, 36(3): 465-475. DOI: 10.1097/iae.0000000000000645.
25. Coscas G, De Benedetto U, Coscas F, et al. Hyperreflective dots: a new spectral-domain optical coherence tomography entity for follow-up and prognosis in exudative age-related macular degeneration[J]. Ophthalmologica, 2013, 229(1): 32-37. DOI: 10.1159/000342159.
26. Xia Y, Feng N, Hua R. "Choroidal caverns" spectrum lesions[J]. Eye (Lond), 2021, 35(5): 1508-1512. DOI: 10.1038/s41433-020-1074-y.
27. Sakurada Y, Leong BCS, Parikh R, et al. Association between choroidal caverns and choroidal vascular hyperpermeability in eyes with pachychoroid diseases[J]. Retina, 2018, 38(10): 1977-1983. DOI: 10.1097/IAE.0000000000002294.
28. Guo X, Zhou Y, Gu C, et al. Characteristics and classification of choroidal caverns in patients with various retinal and chorioretinal diseases[J/OL]. J Clin Med, 2022, 11(23): 6994[2022-11-26]. https://pubmed.ncbi.nlm.nih.gov/36498569/. DOI: 10.3390/jcm11236994.
29. Biesemeier A, Taubitz T, Julien S, et al. Choriocapillaris breakdown precedes retinal degeneration in age-related macular degeneration[J]. Neurobiol Aging, 2014, 35(11): 2562-2573. DOI: 10.1016/j.neurobiolaging.2014.05.003.
30. Holz FG, Sadda SR, Staurenghi G, et al. Imaging protocols in clinical studies in advanced age-related macular degeneration: recommendations from classification of atrophy consensus meetings[J] Ophthalmology, 2017, 124(4): 464-478. DOI: 10.1016/j.ophtha.2016.12.002.
31. Ferris FL 3rd, Wilkinson CP, Bird A, et al. Clinical classification of age-related macular degeneration[J]. Ophthalmology, 2013, 120(4): 844-851. DOI: 10.1016/j.ophtha.2012.10.036.
32. Wong CW, Yanagi Y, Lee WK, et al. Age-related macular degeneration and polypoidal choroidal vasculopathy in Asians[J]. Prog Retin Eye Res, 2016, 53: 107-139. DOI: 10.1016/j.preteyeres.2016.04.002.
33. Srivastava SK, Csaky KG. Identification of well-defined intrachoroidal neovascularization by high-speed indocyanine green angiography[J]. Retina, 2003, 23(5): 712-714. DOI: 10.1097/00006982-200310000-00019.
34. Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: consensus on neovascular age-related macular degeneration nomenclature study group[J]. Ophthalmology, 2020, 127(5): 616-636. DOI: 10.1016/j.ophtha.2019.11.004.
35. Fragiotta S, Parravano M, Costanzo E, et al. Subretinal lipid globules an early biomarker of macular neovascularization in eyes with intermediate age-related macular degeneration[J/OL]. Retina, 2023, 2023: E1 (2013-02-07)[2023-09-11]. https://pubmed.ncbi.nlm.nih.gov/36763979/. DOI: 10.1097/IAE.0000000000003760. [published online ahead of print].
36. Kohno H, Sakai T, Saito S, et al. Treatment of experimental autoimmune uveoretinitis with atorvastatin and lovastatin[J]. Exp Eye Res, 2007, 84(3): 569-576. DOI: 10.1016/j.exer.2006.11.011.
37. Diaz-Llopis M, Gallego-Pinazo R, Garcia-Delpech S, et al. General principles for the treatment of non-infectious uveitis[J]. Inflamm Allergy Drug Targets, 2009, 8(4): 260-265. DOI: 10.2174/187152809789352203.
38. Jabs DA, Nussenblatt RB, Rosenbaum JT, et al. Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop[J]. Am J Ophthalmol, 2005, 140(3): 509-516. DOI: 10.1016/j.ajo.2005.03.057.
39. Begaj T, Yuan A, Lains I, et al. Presence of choroidal caverns in patients with posterior and panuveitis[J/OL]. Biomedicines, 2023, 11(5): 1268[2023-04-25]. https://pubmed.ncbi.nlm.nih.gov/37238939/. DOI: 10.3390/biomedicines11051268.

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