Hyperreflective foci (HRF) is a term coined to depict hyperreflective dots or roundish lesions within retinal layers visualized through optical coherence tomography (OCT). Histopathological correlates of HRF are not univocal, spacing from migrating retinal pigment epithelium cells, lipid‐laden macrophages, microglial cells, and extravasated proteinaceous or lipid material. Despite this, HRF can be considered OCT biomarkers for disease progression, treatment response, and prognosis in several retinal diseases, including diabetic macular edema, age‐related macular degeneration (AMD), retinal vascular occlusions, and inherited retinal dystrophies. The structural features and topographic location of HRF guide the interpretation of their significance in different pathological conditions. The presence of HRF less than 30 μ m with reflectivity comparable to the retinal nerve fiber layer in the absence of posterior shadowing in diabetic macular edema indicates an inflammatory phenotype with a better response to steroidal treatment. In AMD, HRF overlying drusen are associated with the development of macular neovascularization, while parafoveal drusen and HRF predispose to macular atrophy. Thus, HRF can be considered a key biomarker in several common retinal diseases. Their recognition and critical interpretation via multimodal imaging are vital to support clinical strategies and management.

Glaucoma is a group of optic neuropathies characterized by a progressive degeneration of retina ganglion cells (RGCs) and their axons that precedes functional changes detected on the visual field. The macular ganglion cell complex (GCC), available in commercial Fourier-domain optical coherence tomography, allows the quantification of the innermost retinal layers that are potentially involved in the glaucomatous damage, including the retinal nerve fiber (RNFL), ganglion cell and inner plexiform layers. The average GCC thickness and its related parameters represent a reliable biomarker in detecting preperimetric glaucomatous damage. The most accurate GCC parameters are represented by average and inferior GCC thicknesses, and they can be associated with progressive visual field loss. Although the diagnostic accuracy increases with more severe glaucomatous damage and higher signal strength values, it is not affected by increasing axial length, resulting in a more accurate discrimination of glaucomatous damage in myopic eyes with respect to the traditional RNFL thickness. The analysis of the structure-function relationship revealed a good agreement between the loss in retinal sensitivity and GCC thickness. The use of a 10-2° visual field grid, adjusted for the anatomical RGCs displacement, describes more accurately the relationship between RGCs thickness and visual field sensitivity loss.

Background/aims To study the multimodal imaging findings of a large series of eyes with cilioretinal artery obstruction (CILRAO) and describe the systemic associations. Methods Multicentre, retrospective chart review from 12 different retina clinics worldwide of eyes with CILRAO, defined as acute retinal whitening in the distribution of the cilioretinal artery, were identified. The clinical, systemic information and multimodal retinal imaging findings were collected and analysed. Results A total of 53 eyes of 53 patients with CILRAO were included in the study. In 100% of eyes, fundus photography illustrated deep retinal whitening corresponding to the course of the cilioretinal artery. Twenty-eight patients (52.8%) presented with isolated CILRAO (baseline best-corrected visual acuity (BCVA) 20/50, final BCVA 20/25) associated with nocturnal hypotension, 23 patients (43.4%) with CILRAO secondary to central retinal vein occlusion (CRVO) (baseline BCVA 20/40, final BCVA 20/20) and two patients with CILRAO due to biopsy-proven giant cell arteritis (GCA) (baseline BCVA 20/175, final BCVA 20/75). With spectral domain optical coherence tomography (SD-OCT), a hyper-reflective band involving the inner nuclear layer (ie, paracentral acute middle maculopathy or PAMM) was noted in 51 eyes (28/28 eyes with isolated CILRAO and 23/23 eyes with CILRAO+CRVO) corresponding to the retinal whitening. In the two eyes with CILRAO+GCA, SD-OCT illustrated hyper-reflective ischaemia of both the middle and inner retina. Conclusions Isolated CILRAO and CILRAO secondary to CRVO are the result of hypoperfusion or insufficiency, rather than occlusion, of the cilioretinal artery and are associated with PAMM or selective infarction of the the inner nuclear layer. With GCA, there is complete occlusion of the cilioretinal artery producing ischaemia involving both the middle and inner retina associated with worse visual outcomes.

Purpose: To investigate the association between choroidal caverns, choroidal vascular hyperpermeability (CVH), and pachyvessels in eyes with pachychoroid disease. Methods: This was a retrospective review of swept-source optical coherence tomography and indocyanine green angiography imaging performed on eyes with pachychoroid disease. Results: Imaging from 21 eyes with pachychoroid disease entities (8 eyes with pachychoroid pigment epitheliopathy, 11 eyes with central serous chorioretinopathy, and 3 eyes with pachychoroid neovasculopathy) from 11 patients (mean 49.5 years, male/female: 10/1, all white) was available for review. In all study eyes, pachyvessels traversed the areas of CVH visible in mid- and late-phase indocyanine green angiography. A total of 504 choroidal caverns were identified in 11 study eyes (52%). Of the 504 choroidal caverns, 445 (88%) were seen within the areas of CVH compared with 59 (12%), which were detected outside the areas of CVH (P < 0.001). Eyes with multiple caverns had an increased choroidal thickness when compared with eyes with ≤1 cavern (P < 0.001). Conclusion: Choroidal caverns, found primarily in the areas of indocyanine green angiography CVH traversed by pachyvessels, were detected in 52% of eyes with pachychoroid disease. The presence of choroidal caverns in these cases may indicate a loss of normal choroidal architecture associated with dilated Haller layer veins and increased choroidal thickness.

Recent evidence indicates that neurodegeneration is a critical element of diabetic retinopathy (DR) pathogenesis. The neuronal cells’ apoptosis contributes to microvascular impairment and blood–retinal barrier breakdown. Therefore, neurodegeneration represents an early intervention target to slow and prevent the development of microvascular alterations visible on clinical examination. Multimodal imaging features and functional assessment can permit the identification of neuronal damage in a subclinical stage before the recognition of DR signs. Clinical features of neurodegeneration are crucial in identifying patients at high risk of developing a vascular impairment and, thus, serve as outcome measures to understand the efficacy of supplementation. The optimal approach for targeting neurodegeneration contemplates the use of topical compounds that possibly act on different elements of the pathogenic cascade. To date, clinical trials available on humans tested three different topical agents, including brimonidine, somatostatin, and citicoline, with promising results.

Purpose: To investigate the risk factors predictive for the development of neovascular age-related macular degeneration (NVAMD) by means of spectral-domain optical coherence tomography. Methods: Retrospective study of 73 eyes graded Stage 2 and Stage 3 according to the AMD International Grading System with minimum follow-up of 24 months. Drusenoid pigment epithelial detachment, hyperreflective foci, external limiting membrane, inner ellipsoid band, and retinal pigment epithelium integrity were analyzed at baseline and last follow-up. Binary logistic regression model analyzed significant predictors of neovascular conversion. Results: The discontinuity of external limiting membrane, inner ellipsoid band, and retinal pigment epithelium bands were significantly more prevalent in the NVAMD group at baseline and last follow-up (P < 0.001). Hyperreflective foci represented the single most important predictor of neovascular conversion (Exp [B], 15.15; P = 0.005) as confirmed by Kaplan–Meier curve (P = 0.002). Drusenoid pigment epithelial detachment width was significantly greater in NVAMD group than control subjects at baseline and last follow-up (P < 0.001), and its delta value also resulted a significant neovascular predictor (Exp [B], 0.99; P = 0.04). Conclusion: Hyperreflective foci significantly increase the risk of NVAMD progression. The delta width of drusenoid pigment epithelial detachment also predicts disease progression, integrating the stratification of NVAMD progression risk.