Autoimmune retinopathy (AIR) is a rare and still poorly understood immune-mediated disease that may cause inflammation from circulating autoantibodies against the retina. It may be related to history of autoimmune disease in the patient or in a family member or the presence of neoplastic disease in the individual. The disease may be subdivided into paraneoplastic and non-paraneoplastic AIR. When related to melanoma, it is referred to as MAR, and when related to other cancers, it is called CAR. The exact prevalence of AIR is unknown. It mainly affects older adults. Patients present with bilateral and asymmetric scotomas, photopsias, visual field defects, with rapidly progressive visual loss in late onset. In the initial stage, fundus examination is unremarkable, and in late stages, there is limited retinal epitheliopathy and vascular attenuation, with or without optic disc pallor, associated or not with intraocular inflammation and with no evidence of degenerative retinal disease. A clinical investigation with detailed anamnesis and laboratory tests should be performed to search for an associated neoplasm. Ophthalmologic and complementary examinations such as full-field electroretinogram, optical coherence tomography, visual field and fundus autofluorescence, help the diagnosis. Blood tests to search for autoantibodies should be requested. Management consists of prolonged immunosuppression, which may be combined with antioxidant vitamins. In general, the prognosis is uncertain, so the disease still needs to be better understood. More studies should be performed to improve diagnostic measures and define specific management that could preserve or even restore vision.

GUCY2D encodes retinal guanylate cylase-1 (retGC1), a protein that plays a pivotal role in the recovery phase of phototransduction. Mutations in GUCY2D are associated with a leading cause of recessive Leber congenital amaurosis (LCA1). Patients present within the first year of life with aberrant or unrecordable electroretinogram (ERG), nystagmus and a relatively normal fundus. Aside from abnormalities in the outer segments of foveal cones and, in some patients, foveal cone loss, LCA1 patients retain normal retinal laminar architecture suggesting they may be good candidates for gene replacement therapy. Several animal models of LCA1, both naturally occurring and engineered, have been characterized and provide valuable tools for translational studies. This mini-review will summarize the phenotypes of these models and describe how each has been instrumental in proof of concept studies to develop a gene replacement therapy for GUCY2D-LCA1.

BACKGROUND: Persistent subretinal fluid after rhegmatogenous retinal detachment (RRD) surgery is responsible for delayed recovery, and may affect the final visual outcome. Cause, consequences, and treatment remain elusive.
METHODS: Literature review and case series.
METHODS: We reviewed the pathophysiological principles and therapeutic options from the literature, and we report the results from a subretinal fluid cytology study. Nine eyes from nine patients with macula-involving RRD underwent surgical repair. The cellular content of subretinal fluid (SRF) was studied by electron microscopy and anti-rhodopsin immunostaining. All eyes were assessed postoperatively with optical coherence tomography for the detection of persistent submacular fluid (PSF) (Ethics Committee Ghent University Hospital, registration number B6702006169).
RESULTS: Certain patient characteristics as well as surgical methods were implicated. PSF appears to occur more frequently in patients with longstanding detachments treated with buckling surgery. Several therapeutic options have been suggested but safety and efficacy remain unclear. We found PSF in three eyes on postoperative OCT scans, which corresponded to the three cell-rich subretinal samples.
CONCLUSIONS: PSF after successful RRD repair seems to be related to fluid composition. We hypothesize, in the absence of an effective treatment, that a modified surgical drainage, including a washout of the subretinal space, could evacuate the subretinal fluid more completely, and may prevent this complication.

OBJECTIVE: To review the pathophysiologic principles underlying increased autofluorescence from the outer retina and subretinal space using selected diseases as examples.
METHODS: The ocular imaging information and histopathologic features, when known, were integrated for diseases causing increased autofluorescence from the outer retina and subretinal space. Inferences were taken from this information and used to create a classification scheme.
RESULTS: These diseases are principally those that cause separation of the outer retina from the retinal pigment epithelium, thereby preventing proper phagocytosis of photoreceptor outer segments. The separation can arise from increased exudation into the subretinal space or inadequate removal of fluid from the subretinal space. Lack of normal outer segment processing initially leads to increased accumulation of outer segments on the outer retina and subretinal space. Over time, this material is visible as an increasingly thick coating on the outer retina, is yellow, and is autofluorescent. Over time, atrophy develops with thinning of the deposited material and decreasing autofluorescence. The accumulated material is ultimately capable of inducing damage to the retinal pigment epithelium. Diseases causing accumulation of the material include central serous chorioretinopathy, vitelliform macular dystrophy, acute exudative polymorphous vitelliform maculopathy, choroidal tumors, and vitreomacular traction syndrome.
CONCLUSIONS: The physical separation of the retinal outer segments from the retinal pigment epithelium hinders proper phagocytosis of the outer segments. Accumulation of the shed but not phagocytized outer segments plays a role in disease manifestations for a number of macular diseases.

The gene ABCA4 encodes the rod and cone photoreceptor Rim protein, which is a transmembrane transporter of vitamin A intermediates. ABCA 4 mutations are responsible for a large variety of retinal degenerations including all cases of Stargardt macular dystrophy and fundus flavimaculatus, some forms of cone-rod degeneration, and retinitis pigmentosa, and likely increase the risk of developing age-related macular degeneration (AMD). The purpose of this mini-review is to highlight the advances in our understanding of Stargardt disease and the ABCA4 gene from the first description of the disease by Karl Stargardt in 1909 to gene discovery by Allikmets and colleagues in 1997. The knockout mouse model by Mata and co-workers has provided crucial pathophysiological information that has led to new ideas regarding treatment possibilities. These hypotheses were tested by Radu and colleagues in the mouse and shown to be efficacious.

Recent evidence suggests that the adult mammalian retina is far more plastic than was previously thought. Retinal detachment induces changes beyond the degeneration of outer segments (OS). Changes in photoreceptor synapses, second- and even third-order neurons may all contribute to imperfect visual recovery that can occur after successful reattachment. Changes that occur in Müller cells have obvious effects through subretinal fibrosis and proliferative vitreoretinopathy, but other unidentified effects seem likely as well. Reattachment of the retina induces its own set of responses aside from OS re-growth. Reattachment halts the growth of Müller cell processes into the subretinal space, but induces their growth on the vitreal surface. It also induces the outgrowth of rod axons into the inner retina.

Accumulation of lipofuscin is one of the most characteristic features of ageing observed in retinal pigment epithelial (RPE) cells. The lipofuscin found in RPE cells differs from that of other body tissues due to the fact that it is mainly derived from the chemically modified residues of incompletely digested photoreceptor outer segments. It is a heterogeneous material composed of a mixture of lipids, proteins, and different fluorescent compounds, the main fluorophore of which has recently been identified as a derivative of vitamin A. Research interest has variously focussed on the roles of age, light damage, free radicals, antioxidants, visual pigments, retinal locus, lysosomal enzymes, and pigmentation on lipofuscin formation, as well as the effects of lipofuscin on RPE cell function and causation of retinal disease. This article reviews the recent advances in knowledge of the composition, origin, and possible deleterious effects of RPE cell lipofuscin.