Age-related macular degeneration eyes showing cuticular drusen and reticular pseudodrusen

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The clinical records of patients diagnosed with CD or DPR at the Retina Clinic, Samsung Medical Center, Seoul, Korea, between January 2010 and December 2020 were retrospectively reviewed. We first searched the medical records of patients over the age of 50 diagnosed with CD or RPS. Among them, patients who underwent multimodal imaging were included in the study if they met the diagnostic criteria for CD and PDR described below. Cases with poor image quality due to media opacity such as lens opacity were excluded. Exclusion criteria also included traumatic, inflammatory and hereditary retinal disorders.

Demographic information, including age, gender, ocular and systemic comorbidities, and medical history, was obtained for each patient. All patients underwent a comprehensive ophthalmic examination, including measurement of best corrected visual acuity (BCVA), overt refractive error, slit lamp biomicroscopy, and fundus examination.

Institutional Review Board approval was obtained from the Institutional Review Board of Samsung Medical Center, and the study was conducted in accordance with the principles of the Declaration of Helsinki. Given the retrospective nature of the study and the use of anonymized data, the informed consent requirement was waived by the institutional review board.

Imaging analysis

Patients underwent multimodal imaging including CFP (TRC 50 IX, Topcon, Tokyo, Japan), RF, NIR, FAF, spectral domain optical coherence tomography (Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg, Germany) and optical scanning coherence tomography (DRI OCT Triton, Topcon, Tokyo, Japan). In SD-OCT, two B-scans centered on the fovea (horizontal and vertical, length 30 degrees, ART 100) and one volume scan (square 30 × 30 degrees centered on the fovea, 31 horizontal B-scans, ART 25 ) have been obtained. In SS-OCT, two B-scans centered on the fovea (horizontal and vertical, 12 mm, ART 100) and a volume scan (12 × 9 mm square centered on the fovea, 256 horizontal B-scans, ART 4) were been obtained. FA, ICGA (Spectralis HRA + OCT or Optos 200Tx, Optos PLC, Dunfermline, UK) and UWF (Optos 200Tx) photographs were also taken. The morphological and topographic characteristics of CD and RPD were assessed by two investigators (JMY and DHS), and in case of disagreement, a senior interpreter (DIH) made the final decision.

The presence of soft drusen, large drusen, MNV, GA, drusenoid pigment epithelial detachment (drusenoid PED), and acquired vitelliform lesion (AVL) were determined as follows. Soft drusen are yellowish-white raised deposits (>63 µm in size) with a slightly blurred boundary in the CFP, showing none to minimal hyperfluorescence in later stages of FA. They appear as domed elevations of the retinal pigment epithelium (RPE) with homogeneous, moderately reflective inner material in OCT. Large drusen were defined as drusen larger than 200 μm, showing RPE elevations in OCT23. GA was defined as a sharply demarcated hypopigmented area with large choroidal vessels visible in the CFP and hypoautofluorescent in the FAF, with a diameter of at least 175 μm. Drusenoid PED was defined as a diameter ≥½ confluent soft drusen disc below the center of the macula29. The VL was defined as yellowish subretinal material in color photography and hyperautofluorescence in the FAF, corresponding to a dome-shaped hyperreflective material between the ellipsoid area and the RPE-basal lamina-Bruch membrane band in OCT30.31.

AMD has been classified according to the clinical classification system by the Beckman Initiative Classification Committee for Macular Research. The definition and classification of NVMs followed the criteria proposed by the CONAN study group (Concensus on Neovascular Age-related macular degeneration Nomenclature).

Diagnosis and distribution of cuticular drusen

The diagnostic criteria for CD used in this study are described in detail elsewhere.15. Briefly, MCs were defined as multiple yellow or pale, small, round lesions seen in the CFP, showing a symmetrical distribution pattern between bilateral eyes. There must have been at least 50 scattered, uniformly sized, small (25‒75 μm) hyperfluorescent drusen with a typical “stars in the sky” appearance on FA images in each eye2.5. The lesion must have been located below the RPE, with elevation of the RPE on the OCT images2.32.

Fundus topographic distribution patterns of DC were classified as either macular or diffuse, based on PSC and FA findings. The macular type was defined as drusen distributed only in the major vascular arcades, while the diffuse type was defined as drusen involving the macula, but also extending beyond the vascular arcades.2.

Diagnosis and distribution of reticular pseudodrusen

Diagnosis of RPD was based on appropriate findings: (1) multiple yellowish-white lesions with a reticular network in CFP, (2) interlaced network in RF imaging, (3) hyporeflective lesions with slight background hyperreflectance in NIR imaging, ( 4) hypofluorescent lesions against a background of mild hyperfluorescence on FAF imaging, (5) ≥5 hyperreflective subretinal deposits above the RPE on more than one b-scan image on OCT, and (6) hypofluorescent lesions in the middle or late phase of ICGA. RPDs were defined as definitive if identified using at least three imaging methods, including OCT.

The fundus topographic distribution pattern of RPD has been categorized into localized, intermediate, or diffuse types based on the extent of involvement of the retinal areas according to criteria described elsewhere.9.

Additionally, SDD variants were defined as deposits with features similar to RPD except for hyperautofluorescence on FAF imaging11.

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