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PurposeTo describe acute and chronic retinal ischemic changes following an internal carotid artery pseudoaneurysm stenting procedure, and to review current evidence for risk factors and management of post-procedural retinal ischemic events.ObservationA 50-year-old man presented with a 3-month history of pulsatile tinnitus, headache, and intermittent blurry vision. A CT angiogram of head and neck showed bilateral cervicopetrous internal carotid artery (ICA) pseudoaneurysms. The patient underwent successful repair with angioplasty and stenting of the flow-limiting high-grade (>95%) stenosis of his left high cervical ICA. On post-operative day 1, the patient reported monocular vision loss with a large central scotoma. He was found to have a central macular area of retinal whitening and multiple areas of perivascular retinal whitening on exam, concerning for retinal artery occlusions secondary to peri-procedural emboli. Dual antiplatelet therapy was started and a stroke evaluation was performed. Two months later, his visual acuity in the affected eye was counting fingers and his left eye fundus examination was notable for multiple areas of scattered hemorrhages, microaneurysms, and retinal exudates in the distribution of prior retinal ischemia. OCT imaging revealed atrophic changes in the left macula. Subsequently, the patient completed stage-2 repair of the left ICA pseudoaneurysm followed by uncomplicated repair of the right ICA. Four months later, his left eye visual acuity and retinal findings remained stable.Conclusions and importancePost-procedure retinal emboli and ischemia are important, vision threatening possible ocular complications for patients undergoing carotid vascular and endovascular procedures.

Background/aimsCurrent retinoblastoma staging systems do not adequately describe the disease, especially in eyes with multiple tumors. The aims of this study were to develop methods for documenting individual tumors and to score disease burden over time.MethodsA coding system was devised to describe each tumor according to affected eye, meridian, anteroposterior location, activity, growth pattern, type of seed, and treatment. A scoring system for quantifying disease burden was developed, taking account of tumor number, size, spread, and secondary effects on the eye.ResultsOur coding system allowed contemporaneous tumor documentation, producing datasets that enabled generation of fundus diagrams, Kaplan-Meier curves, and tables summarizing disease progression in individual tumors and eyes. Our data showed disparities between ocular and tumor documentation, e.g., indicating earlier tumor development in the left eye but younger age at presentation if disease was worse in the right eye. Actuarial rates of local treatment failure were lower when individual tumors were analyzed than when data were reported in terms of whole eyes.ConclusionOur methods for documenting individual retinoblastomas have facilitated the review of patients' progress in our routine practice and may provide data that could be used to refine retinoblastoma classifications in the future.

PurposeTo report a case of metastatic cutaneous melanoma presenting with choroidal metastasis simulating primary uveal melanoma.DesignCase report.MethodPresentation of clinical, radiographic, histopathologic, and tumor genetic findings in a patient with cutaneous melanoma with choroidal metastasis.ResultsA 50-year-old man with a remote history of stage 1A cutaneous melanoma presented with eye pain, peripheral vision loss, floaters, red eye, and choroidal mass that was originally diagnosed as a primary uveal melanoma at an outside institution; however, subsequent imaging and clinical evaluation demonstrated that this choroidal mass was the first manifestation of widely metastatic cutaneous melanoma (liver, pancreas, lung, bone, brain, and orbit lesions). Histopathologic analysis of the tumor after enucleation was consistent with cutaneous melanoma, and tumor genetic testing was positive for BRAF V600E mutation, confirming the choroidal lesion to be a cutaneous melanoma metastasis rather than a primary choroidal melanoma.ConclusionsMetastatic cutaneous melanoma to the orbit or globe occurs rarely. Tumor genetic testing may help differentiate metastatic cutaneous melanoma from primary uveal melanoma in cases where the diagnosis is uncertain, and can also inform therapy and prognostic counseling.

Variants in HGSNAT have historically been associated with syndromic mucopolysaccharidosis type IIIC (MPSIIIC) but more recent studies demonstrate cases of HGSNAT-related non-syndromic retinitis pigmentosa. We describe and expand the genotypic and phenotypic spectrum of this disease. This is a retrospective, observational, case series of 11 patients with pericentral retinitis pigmentosa due to variants in HGSNAT gene without a syndromic diagnosis of MPSIIIC. We reviewed ophthalmologic data extracted from medical records, genetic testing, color fundus photos, fundus autofluorescence (FAF), and optical coherence tomography (OCT). Of the 11 patients, the mean age was 52 years (range: 26–78). The mean age of ophthalmologic symptoms onset was 45 years (range: 15–72). The visual acuity varied from 20/20 to 20/80 (mean 20/30 median 20/20). We described five novel variants in HGSNAT: c.715del (p.Arg239Alafs *37), c.118 G>A (p.Asp40Asn), c.1218_1220delinsTAT, c.1297A>G (p.Asn433Asp), and c.1726 G>T (p.Gly576*). HGSNAT has high phenotypic heterogeneity. Data from our cohort showed that all patients who had at least one variant of c.1843 G>A (p.Ala615Thr) presented with the onset of ocular symptoms after the fourth decade of life. The two patients with onset of ocular symptoms before the fourth decade did not carry this variant. This may suggest that c.1843 G>A variant is associated with a later onset of retinopathy. [ABSTRACT FROM AUTHOR]

The BEST1 gene encodes bestrophin-1, a homopentameric ion channel expressed in the retinal pigment epithelium (RPE), where it localizes to the basolateral plasma membrane. Pathogenic variants in this gene can cause different autosomal dominant and recessive inherited retinal diseases (IRDs), collectively named "bestrophinopathies." These disorders share a number of clinical and molecular features that make them an appealing target for gene therapy. Clinically, bestrophinopathies are often slowly progressive with a wide window of opportunity, and the presence of subretinal material (vitelliform deposits and/or fluid) as a hallmark of these conditions provides an easily quantifiable endpoint in view of future clinical trials. From a molecular standpoint, most BEST1 pathogenic variants have been shown to cause either loss of function (LOF) of the protein or a dominant-negative (DN) effect, with a smaller subset causing a toxic gain of function (GOF). Both LOF and DN mutations may be amenable to gene augmentation alone. On the other hand, individuals harboring GOF variants would require a combination of gene silencing and gene augmentation, which has been shown to be effective in RPE cells derived from patients with Best disease. In this article, we review the current knowledge of BEST1-related IRDs and we discuss how their molecular and clinical features are being used to design novel and promising therapeutic strategies. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa GTPase regulator (RPGR)-related retinopathy is a retinal dystrophy inherited in a X-linked recessive manner that typically causes progressive visual loss starting in childhood with severe visual impairment by the fourth decade of life. It manifests as an early onset and severe form of retinitis pigmentosa. There are currently no effective treatments for RPGR-related retinopathy; however, there are multiple clinical trials in progress exploring gene augmentation therapy aimed at slowing down or halting the progression of disease and possibly restoring visual function. This review focuses on the molecular biology, clinical manifestations, and the recent progress of gene therapy clinical trials. [ABSTRACT FROM AUTHOR]

The nonsynonymous variants of lipid phosphatase (FIG4) in patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) is described. Heterozygosity for a deleterious allele FIG 4 that regulates PI(3,5)[P.sub.2] is found to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.