Response to treatment with intravitreal anti-vascular endothelial growth factors in bilateral exudative cuticular drusen.

PURPOSE: To present the response to treatment with anti-vascular endothelial growth factor (VEGF) agents of exudative cuticular drusen (CD) in a patient who developed temporary suspended scattering particles in motion (SSPiM) after injection in the symptomatic eye and full recovery of subretinal hyperreflective exudation (SHE) in the fellow eye by multimodal imaging modalities. OBSERVATIONS: A 46-year-old patient was diagnosed with exudative CD associated with type I and II (mixed type) macular neovascularization (MNV) in the right eye, and quiescent type I MNV was detected in the left eye by en face optical coherence tomography angiography (OCTA). Bilateral flat irregular pigment epithelial detachments were found in both eyes by optical coherence tomography (OCT). A week after injection of intravitreal aflibercept (IVA), oval shaped hypersignals developed at Henle's fiber layer with a petaloid appearance and at the subfoveal space as detected by en face OCTA in the right eye. These oval hypersignals were considered as SSPiM. They disappeared 4 weeks later and did not recur. During follow-up of the patient, juxtafoveal SHE and disruption of the ellipsoid zone (EZ) were noticed in her left asymptomatic eye by OCT. Fluorescein angiography disclosed leakage at the location of the SHE. Choriocapillaris flow analyzed by cross-sectional OCTA disclosed time-dependent local alterations before and after the development of SHE. SHE recurred twice, and juxtafoveal type I MNV subsequently developed at the same location. Intravitreal ranibizumab (IVR) treatment was initiated because of distorted vision accompanied by the development of SHE and persistent subfoveal fluid accumulation, as documented by OCT during IVA treatment. Complete recovery of the EZ took place consistently in both eyes with stable vision over three years of follow-up. CONCLUSIONS AND IMPORTANCE: Temporary SSPiM could be seen in the early period after IVA injection once but has not recurred up to three years' follow-up in the right eye of our patient with exudative CD. Prompt and appropriate treatment of SHE by intravitreal anti-VEGF agents (IVA and IVR) prevented the permanent deterioration of visual acuity in the left eye with type I MNV at her thirty-months follow-up.

Novel recessive cone-rod dystrophy caused by POC1B mutation.

IMPORTANCE: A new form of cone-rod dystrophy (CORD) is described and the gene responsible for the disease is identified. OBJECTIVE: To clinically evaluate 4 patients and 5 control relatives, perform disease gene mapping, and identify the gene defect responsible for CORD. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational case series of 13 members of a consanguineous family and 113 unrelated control individuals. INTERVENTIONS: Clinical investigations included eye examination with color fundus and autofluorescent imaging, spectral-domain optical coherence tomography, and electrophysiologic measurements. Linkage mapping was performed using single-nucleotide polymorphism genotype data. Candidate genes were analyzed for mutations via Sanger sequencing. MAIN OUTCOMES AND MEASURES: Clinical diagnosis of CORD, disease gene mapping, and mutation identification. RESULTS: The onset of CORD occurred in early childhood. The clinical phenotype was typical CORD with photophobia, decreased central vision, and dyschromatopsia. In all patients, a disrupted inner segment/outer segment line and the external limiting membrane were noted as a single blurry line at the central fovea, and the cone outer segment tip line was absent. In the midperipheral retina, the rod inner segment/outer segment line was disrupted and blurry, and the rod outer segment tip line was absent. Cone response was nonrecordable in all patients, whereas rod response was nonrecordable in the eldest patient and subnormal in the others. The Arden Index was abnormal in the youngest patient and flat in the others. The disease gene mapped to a less than 2-megabase recessive locus at 12q21.33 with a logarithm of odds score of 3.92. At the locus, we identified a homozygous missense POC1B p.R106P mutation that was predicted as damaging by online tools. CONCLUSIONS AND RELEVANCE: POC1B is a novel gene for a new disease typical of CORD except that patients did not report night blindness. The clinical course was slowly progressive. Screening for POC1B mutation could benefit families afflicted with CORD.

A novel recessive GUCY2D mutation causing cone-rod dystrophy and not Leber's congenital amaurosis.

Cone-rod dystrophies are inherited retinal dystrophies that are characterized by progressive degeneration of cones and rods, causing an early decrease in central visual acuity and colour vision defects, followed by loss of peripheral vision in adolescence or early adult life. Both genetic and clinical heterogeneity are well known. In a family with autosomal recessive cone-rod dystrophy, genetic analyses comprising genome scan with microsatellite markers, fine mapping and candidate gene approach resulted in the identification of a homozygous missense GUCY2D mutation. This is the first GUCY2D mutation associated with autosomal recessive cone-rod dystrophy rather than Leber's congenital amaurosis (LCA), a severe disease leading to childhood blindness. This study hence establishes GUCY2D, which is a common cause for both recessive LCA and dominant cone-rod dystrophy, as a good candidate for autosomal recessive cone-rod dystrophy.