Presence of Hyper-Reflective Layer Linked to Poor Visual Prognosis in nAMD

Retinal pigment epithelial detachment. Ophthalmoscope view of the retina in a case of pigment epithelial detachment (PED). This condition occurs when fluid beneath the retinal pigment epithelium (RPE) causes detachment (circular area at left). The macula of the retina (left) is the area affected by the PED. The optic disc of the retina is at right where the blood vessels are converging. PED is associated with age-related macular degeneration and central serous choroidopathy. It can resolve without treatment, but may require drugs and laser therapy to repair the damage. For fluorescent angiography views of this retina, see images C025/7690 and C025/7926.
Researchers explain spectral-domain OCT findings for these patients and the impact of anti-VEGF therapy.

Multilayer pigment epithelial detachment in neovascular age-related macular degeneration (nAMD) with a homogenous, strongly hyper-reflective layer is associated with worse visual prognosis in patients, according to research published in the British Journal of Ophthalmology. 

To investigate the structure of multilayered pigment epithelial detachment in nAMD as well as its association with visual prognosis and fibrotic scar progression, researchers conducted a retrospective analysis of patients treated at the Yeungnam University Medical Center in South Korea between January 2016 and February 2020. Patients with multilayered pigment epithelial detachment with a prechoroidal cleft secondary to nAMD were included in the study. 

Morphologic structures within the sub-pigment epithelial detachment were analyzed and divided into 3 layers: the first (layer 1) included the inhomogeneous, weak hyper-reflective space between the hyper-reflective band and the retinal pigment epithelium (RPE). The second (layer 2) was the strong homogenous hyper-reflective band, and the third (layer 3) — defined as a prechoroidal cleft — was the hyporeflective space between the hyper-reflective band and Bruch’s membrane. 

The cohort included 68 eyes from 63 patients. Among these eyes, 55.9% were classified as having layer 2, with significant choroidal neovascularization subtypes noted among the subgroups. Baseline best corrected visual acuity (BCVA) was 0.55 (±0.25) in the group with layer 2, compared with 0.42 (±0.29) in the group without layer 2. No substantial difference in external limiting membrane status and ellipsoidal zone integrity were noted. 

Within the group with layer 2, the number of antivascular endothelial growth factor (anti-VEGF) injections after the occurrence of a prechoroidal cleft was 8.5 (±6.2) in those with layer 2 vs 8.3 (±5.6) in the group without layer 2. No significant between-group differences were noted. BCVA improved significantly at every visit in the group without layer 2; within the group with layer 2, BCVA deterioration was significant. Mean BCVA in this group was significantly worse at month 1, 3, 6, 9, and 12 follow-ups. 

A significant increase in layer 2 thickness was noted in both groups. When the increases in thickness were compared, the group with layer 2 experienced a more pronounced increase. In both groups, the thickness of layers 1 and 3 also significantly decreased during the follow-up period, while the thickness of total multilayered pigment epithelial detachment significantly decreased over the course of the follow-up period. 

Over 12 months, investigators saw an increase in the proportion of eyes presenting with photoreceptor disruption in the group with layer 2; no significant difference was noted in those without layer 2. The proportion of eyes with loss of photoreceptor integrity and rates of fibrotic scar formation were also significantly higher in this group. No significant differences were noted in the incidence of subretinal hemorrhage and RPE tear. 

Results of univariate linear regression analyses indicated that the presence of layer 2, baseline BCVA, and layer 2 thickness were all significantly associated with 12-month BCVA. Multivariate regression analyses demonstrated that the presence of both layer 2 and baseline BCVA were predictors of BCVA at 12 months. 

Finally, logistic regression analyses showed that the presence of layer 2, baseline BCVA, layer 2 thickness, and layer 3 thickness were all significantly associated with fibrotic scar formation at 12 months, with the most significant associations noted for layer 2 presence and baseline BCVA

Study limitations include those inherent to retrospective analyses, the absence of a control group, and a lack of histopathological confirmation. 

“There is a need for further prospective research with larger numbers of patients, longer follow-up times, and correlation with histological studies to compare these sub-[RPE] compartmental changes with antifibrotic agents,” the researchers concluded. “We anticipate that understanding the angiofibrotic switch and developing therapeutic approaches for the prevention of fibrotic scars will lead to improvement of visual prognosis of patients with nAMD.”


Kim I, Ryu G, Sagong M. Morphological features and prognostic significance of multilayered pigment epithelium detachment in age-related macular degeneration. Br J Ophthalmol. Published online March 3, 2021. doi:10.1136/bjophthalmol-2020-318616