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.

Pseudoexfoliation syndrome (PES) is a systemic disorder caused by progressive accumulation of extracellular material over various tissues. PES usually determines increased intraocular pressure, changes in the anatomical aspects of the optic nerve, and visual field alterations leading to the diagnosis of pseudoexfoliation glaucoma (PEG). Use of topical medical treatment usually leads to poor results in terms of long-term follow-up but many surgical techniques, such as Argon Laser or Selective Laser Trabeculoplasty, have been proposed for the management of PEG affected patients. The present paper is a review on the pseudoexfoliation syndrome and pseudoexfoliation glaucoma with an update on surgical management.

The phakomatoses have been traditionally defined as a group of hereditary diseases with variable expressivity characterized by multisystem tumors with possible malignant transformation. The Sturge-Weber syndrome, Klippel-Trenaunay syndrome, and the phakomatosis pigmentovascularis have the facial port-wine stain in common. Numerous pathophysiogenetic mechanisms have been suggested such as venous dysplasia of the emissary veins in the intracranial circulation, neural crest alterations leading to alterations of autonomic perivascular nerves, mutation of the GNAO gene in the Sturge-Weber syndrome, PIK3CA mutation in malformative/overgrowth syndromes such as the Klippel-Trenaunay syndrome, and the twin-spotting phenomenon in phakomatosis pigmentovascularis. Other features linked to the port-wine stain and typical to all of the three conditions are glaucoma and choroidal alterations. Glaucoma can be due to malformations of the anterior chamber or high episcleral venous pressure and in phakomatosis pigmentovascularis it can also be associated with angle hyperpigmentation. The choroid can be thickened in all diseases. Furthermore, choroidal melanocytosis in the phakomatosis pigmentovascularis can lead to malignant transformation. Although the multiple pathophysiological mechanisms still require clarification, similarities in ophthalmic manifestations make it reasonable to classify these diseases in an independent group.

Noteworthy heterogeneity exists in the rare diseases associated with childhood glaucoma. Primary congenital glaucoma is mostly sporadic; however, 10% to 40% of cases are familial. CYP1B1 gene mutations seem to account for 87% of familial cases and 27% of sporadic cases. Childhood glaucoma is classified in primary and secondary congenital glaucoma, further divided as glaucoma arising in dysgenesis associated with neural crest anomalies, phakomatoses, metabolic disorders, mitotic diseases, congenital disorders, and acquired conditions. Neural crest alterations lead to the wide spectrum of iridocorneal trabeculodysgenesis. Systemic diseases associated with childhood glaucoma include the heterogenous group of phakomatoses where glaucoma is frequently encountered in the Sturge-Weber syndrome and its variants, in phakomatosis pigmentovascularis associated with oculodermal melanocytosis, and more rarely in neurofibromatosis type 1. Childhood glaucoma is also described in systemic disorders of mitotic and metabolic activity. Acquired secondary glaucoma has been associated with uveitis, trauma, drugs, and neoplastic diseases. A database research revealed reports of childhood glaucoma in rare diseases, which do not include glaucoma in their manifestation. These are otopalatodigital syndrome, complete androgen insensitivity, pseudotrisomy 13, Brachmann-de Lange syndrome, acrofrontofacionasal dysostosis, caudal regression syndrome, and Wolf-Hirschhorn syndrome.

Purpose: To correlate choroidal thickness (CT) and age with vascularized retinal layer and outer retinal layer thickness in normal eyes. Methods: This was a prospective, cross-sectional study. Complete ophthalmological examination, biometry, and enhanced depth imaging spectral domain optical coherence tomography were performed. Choroidal and individual retinal layer thickness measurements were obtained. Thickness maps for all layers were evaluated using the 1 mm, 3 mm, and 6 mm early treatment diabetic retinopathy study (ETDRS) macular grid areas. Results: One hundred and twenty eyes were included. Choroidal thickness correlated negatively with age in all ETDRS areas. The ganglion cell layer (GCL) in the 1 mm; the GCL and inner plexiform layer (IPL) in the 3 mm and 6 mm; and the GCL, IPL, and inner nuclear layer in the 6 mm areas correlated negatively with age and positively with CT. Retinal nerve fiber layer thickness in the 6 mm area correlated negatively with age. The retinal pigment epithelium-photoreceptor layer in all areas correlated negatively with age and positively with CT. Conclusion: In normal subjects, vascularized retinal layer thicknesses and outer retinal layer thickness correlate positively with CT and negatively with age. The role of neuronal versus vascular components should be considered when evaluating individual retinal layer thicknesses.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder involving aberrant proliferation of multiple tissues of neural crest origin. Retinal vascular alterations in NF1 have rarely been reported in the literature and their nature is not clear. This study describes distinctive retinal microvascular alterations and their relationship to choroidal nodules in patients with neurofibromatosis type 1. This was a retrospective study where records of seventeen consecutive patients with diagnosis of NF1, presenting Lisch nodules and choroidal alterations, and 17 age and gender-matched healthy control patients were evaluated. Fundus photographs, near infrared reflectance and enhanced depth imaging - optical coherence tomography images were reviewed. Retinal microvascular abnormalities and choroidal and retinal alterations in proximity of the retinal microvacular alterations were carefully noted. 6 patients (35%) presented distinctive microvascular abnormalities. These consisted of small, tortuous vessels with a “spiral” or “corckscrew” aspect. They were second or third order, small tributaries of the superior or inferior temporal vein. These vessels were all located overlying choroidal alterations as observed with near infrared reflectance. Enhanced depth imaging - optical coherence tomography showed alteration of choroidal vasculature due to the presence of choroidal nodules but otherwise retinal and choroidal cross-sections were unremarkable for morphology. Retinal microvascular alterations overlying choroidal nodules in patients with NF1 can be considered another distinctive characteristic of the disease. Although the nature of these alterations is not clear, the authors speculate that functional disorders of vasomotor nerve cells, which originate in the embryonal neural crest can lead to their formation.