OCT Speaks Volumes!

Exploring the significance of OCT biomarkers in AMD management

Biomarkers are medical signs that indicate the state of health and wellbeing of an individual objectively. OCT biomarkers help us predict visual acuity (VA) outcomes and treatment response. They play a significant role in patients with AMD by determining progression to advanced AMD, conversion of dry AMD to nAMD, and predicting treatment outcomes and visual prognosis. 1 OCT biomarkers can either be structural (retinal, choroidal, and vitreomacular interface) or based on fluid distribution.

by Dr. Sashwanthi Mohan and Dr. Arthi Mohankumar

Age-related macular degeneration (AMD) is a chronic degenerative condition of the macula and a leading cause of central visual loss worldwide. It is divided into dry and wet AMD or neovascular AMD (nAMD). Optical coherence tomography (OCT) is the most used investigative modality for diagnosis, follow-up, tracking progression, and monitoring treatment of patients with AMD, especially nAMD.

Central retinal thickness

Central retinal thickness (CRT) is one of the first and most common OCT biomarkers for this. However, studies have revealed that CRT alone does not predict visual function well and that certain other biomarkers have better prognostic value.

Drusen

Higher drusen volume is associated with an increased risk of progression to nAMD or geographic atrophy (GA).

The height of drusen is associated with a risk of late atrophic AMD, and the length of drusen is associated with conversion to nAMD.2 OCTreflective drusen substructures (ODS) in eyes with intermediate AMD are associated with a 5.6 risk of progression to GA and not nAMD. Drusen with subretinal fluid (SRF) may represent subclinical choroidal neovascularisation (CNV). Heterogeneous internal reflectivity material within drusen (HIRD) contains hydroxyapatite, an indicator of progression to advanced AMD. Drusenoid PED greater than 2 DD presenting with metamorphopsia have a high risk of progression to GA or nAMD after two years.

Reticular pseudodrusen

Reticular pseudodrusen or subretinal drusenoid deposits (SDD) are located above the retinal pigment epithelium (RPE) and found in the superior macula in 9% to 58% of AMD eyes. Their presence is associated with a two- to six-fold increase in the risk of nAMD or central GA. SDDs located outside the macula are at a higher risk for progression.

Hyperreflective foci

Hyperreflective foci (HRF) are lesions within the retina that can either be found adjacent to the drusen apex or edge in the inner retina. They are strong predictors of AMD progression, with a five-fold high risk of progression to GA at two years. The inner location and cluster distribution of HRF are associated with the development of nAMD.3 HRF on OCT at baseline has a five-times higher risk of progression to GA at two years. In nAMD, HRF regression after anti-VEGF treatment is of good prognostic value for VA.

Outer retinal tubulations

Outer retinal tubulations (ORTs) are ovoid or round hyporeflective lesions with hyperreflective borders at the outer nuclear layer and reflect photoreceptor rearrangement after retinal injury. They are usually present in advanced AMD and are associated with GA or nAMD. The presence of ORTs has been associated with poorer vision in nAMD patients.

Subretinal hyperreflective material

Subretinal hyperreflective material (SHRM) can be fluid, fibrin, scar, blood, or neovascularization. Its presence is associated with worse visual acuity. Subfoveal SHRM with increased height and width is associated with worse visual acuity.

Retinal pigment epithelium rips

Retinal pigment epithelium (RPE) rips are a complication of nAMD which occur in eyes with pigment epithelial detachments (PEDs); either spontaneously or secondary to laser or anti-VEGF therapy. They are associated with poor visual prognosis, especially if there is involvement of the fovea.

RPE and outer retinal atrophy

Abnormal RPE thinning can be associated with the development of atrophic AMD and also signifies the progression of GA when present at its margins. Incomplete retinal pigment epithelial and outer retinal atrophy, or iRora, is loss of outer plexiform and inner nuclear layer forming a hyporeflective wedge and is strongly associated with impending GA. Complete RPE and outer retinal atrophy — cRORA — is the end point of atrophy in the presence of drusen with diameters of 250 mm.

Ellipsoid zone disruption

The ellipsoid zone (EZ) refers to the photoreceptor inner segment/ outer segment (IS/OS) junction on OCT. Disruption of the EZ is said to be associated with progression to advanced AMD — both GA and nAMD. Focal disruption of the RPE, RPE thickening, and irregularities of the retina or external limiting membrane (ELM) are other OCT features that are associated with progression to advanced AMD.

Sub-RPE hyperreflective columns

Hyperreflective columns under the RPE defects are associated with progression to nAMD or GA by three months. These defects affect the integrity of the RPE and allow the growth of new vessels into the subretinal space.

Vitreomacular interface

A higher number of intravitreal anti-VEGF injections is required to manage nAMD in patients with vitreomacular interface abnormalities, but there is no association with VA.

References

Choroidal features

Choroidal thickness measurements below drusen of <135 µm suggest progression to GA. The choroidal thickness was found to have no prognostic value on VA. Early presentation of prechoroidal clefts can have a poor prognosis due to complications, such as RPE rips or hemorrhage. Choroidal caverns do not have any prognostic value.

Neovascular lesions with no fluid

Neovascular lesions on OCT in the absence of fluid are present in 6.25% to 27% of the fellow eyes of nAMD. They are at risk of progression to exudative AMD at one year.4

Is fluid always bad?

Intraretinal fluid in the form of intraretinal cystoid spaces (IRC) (white asterisk in image), correlates with poor VA. It is an important negative biomarker in AMD with an increased risk of development of fibrosis or atrophy and loss of vision. The presence of IRC correlates with poorer visual improvement after anti-VEGF therapy. Whereas, subretinal fluid (SRF) (yellow asterisk in image), if chronic, is said to have a protective effect on VA by protecting photoreceptors from toxic effects of the underlying diseased RPE. The sub-RPE fluid (red asterisk in image) does seem to affect VA prognosis unless associated with IRC or SRF.

Conversion from dry to wet AMD

A thick, double-layer sign (DLS), intraretinal HRF, or exudative macular neovascularization (MNV) in the fellow eye is at higher risk of conversion.5 These OCT signs help identify patients who require frequent monitoring and early treatment.

1. Metrangolo C, Donati S, Mazzola M, et al. OCT Biomarkers in Neovascular Age-Related Macular Degeneration: A Narrative Review. J Ophthalmol. 2021;2021:9994098.

2. Flores R, Carneiro Â, Tenreiro S, Seabra MC. Retinal Progression Biomarkers of Early and Intermediate Age-Related Macular Degeneration. Life (Basel). 2021;12(1):36.

3. Phadikar P, Saxena S, Ruia S, Lai TY, Meyer CH, Eliott D. The potential of spectral domain optical coherence tomography imaging based retinal biomarkers. Int J Retina Vitreous. 2017;3:1.

4. Wakatsuki Y, Hirabayashi K, Yu HJ, et al. Optical Coherence Tomography Biomarkers for Conversion to Exudative Neovascular Age-related Macular Degeneration. Am J Ophthalmol. 2022;247:137-144.

5. Damian I, Nicoară SD. SD-OCT Biomarkers and the Current Status of Artificial Intelligence in Predicting Progression from Intermediate to Advanced AMD. Life (Basel). 2022;12(3):454.

Contributing Doctors

Dr. Sashwanthi Mohan is a specialist ophthalmologist and vitreoretinal specialist at Medcare Eye Centre, Dubai. She completed her DNB Ophthalmology from L.V. Prasad Eye Institute in Hyderabad, India, and was awarded the Dr. G. Venkataswamy Gold Medal for Ophthalmology by the National Board of Examinations, followed by a vitreoretinal fellowship from Sankara Nethralaya, Chennai, where she was awarded as the best outgoing vitreoretinal fellow. She has a keen interest in research and has many peer-reviewed publications to her name. She is also interested in education and has an educational website called Ophthalmobytes. She is a fellow of the international council of Ophthalmology (FICO) and a member of the Royal College of Surgeons, Edinburgh (MRCS).

sashu23@gmail.com

Dr. Arthi Mohankumar is a vitreoretinal surgeon at Rajan Ye Care Hospital, Chennai, India. She has completed her MS in ophthalmology from the Regional Institute of Ophthalmology, Madras Medical College, Chennai, India, and completed her training in medical and surgical retina training at Aravind Eye Hospital, Pondicherry, India. She has a keen interest in research and has multiple peer-reviewed publications in indexed journals. Her areas of interest include diabetic retinopathy, retinopathy of prematurity, and ocular inflammation.

Thus, several OCT features can serve as important biomarkers in tracking progression, conversion, and monitoring response to treatment in patients with AMD. OCT is an important tool that can help the clinician plan an individualized approach for AMD patients. drarthimohankumar@gmail.com