Stellate nonhereditary idiopathic foveomacular retinoschisis and an approach to the differential diagnosis of macular star.

PURPOSE OF REVIEW: This review aims to introduce stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) and its differential diagnosis. We summarize findings from case reports and series published in the last few years on the clinical and imaging findings in SNIFR. RECENT FINDINGS: SNIFR presents as either a unilateral or bilateral macular star on fundus examination without clinical or imaging evidence of exudation or frank vitreomacular traction. optical coherence tomography (OCT) imaging shows schisis cavities in the Henle fibre and outer plexiform layers that correspond to the stellate en face findings. Visual acuity is usually minimally affected, and the presence of significant vision loss should prompt high clinical suspicion for alternate diagnoses. SUMMARY: SNIFR is a recently characterized clinical entity that serves as an important addition to the differential diagnosis of a macular star. It is a diagnosis of exclusion and should be distinguished from other causes of macular star such as neuroretinitis, vitreomacular traction, ocular manifestations of malignant hypertension, congenital juvenile X-linked macular schisis, myopic maculopathy, optic pit maculopathy, nicotinic acid maculopathy or taxane maculopathy among others.

STARGARDT DISEASE: Beyond Flecks and Atrophy.

PURPOSE: To identify changes in the outer retina in areas without atrophy or flecks of Stargardt disease (STGD) using spectral-domain optical coherence tomography. METHODS: Twenty-three STGD patients and 26 control subjects were assessed for outer retina (from the outer border of Bruch membrane [BrM] to the inner border of the inner segment ellipsoid zone [EZ]), BrM-retinal pigment epithelium apex, the EZ thickness, and apical process interdigitation zone. RESULTS: Patients with STGD had increased BrM-EZ thickness in areas without apparent disease versus control subjects at 1,000, 1,500, 2,000, and 2,500 µm superior and 1,500 µm, 2,000 µm, and 2,500 µm inferior to the fovea (P < 0.05 to P < 0.001), greatest difference (3.4 µm) at 2,500 µm superiorly. The BrM-retinal pigment epithelium segment showed larger fractional contribution of 0.48 to 0.51 to the overall BrM-EZ thickness compared with 0.35 to 0.42 in control subjects. The thickness of EZ and the interspace between the retinal pigment epithelium apex and EZ were smaller in the STGD patients (P < 0.05 to P < 0.001). Patients with STGD displayed an interrupted interdigitation zone in 16 (84.2%) of 19 eyes versus 6 (23.1%) of 26 eyes of the control subjects (P < 0.001). The BrM-EZ segment of the outer retina of STGD patients lacked the typical normal trilaminar pattern. CONCLUSION: Subtle changes are present within the BrM-EZ segment of the outer retina of STGD patients in areas that are devoid of atrophy and flecks. These findings suggest that pathologic changes in STGD are more widespread than that seen by clinical examination.

Inner retinal preservation in rat models of retinal degeneration implanted with subretinal photovoltaic arrays.

Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission.

Outcomes in Retinal Vein Occlusions Presenting with Poor Visual Acuity Treated with Anti-Vascular Endothelial Growth Factor Therapy: Prognosis and Predictive Factors.

PURPOSE: To present visual acuity and OCT outcomes in patients with retinal vein occlusion (RVO) treated with anti-vascular endothelial growth factor (VEGF) agents demonstrating poor initial visual acuity. We aimed to identify relevant factors that may portend differential outcomes in this important patient population. DESIGN: Retrospective chart review. PARTICIPANTS: Fifty-two patients with recent RVO treated with anti-VEGF therapy and demonstrating habitual corrected visual acuity of worse than 20/320 before any ocular therapy, with at least 6 months of follow-up. METHODS: Visual acuity, spectral-domain (SD) OCT findings, injection details, and the development of neovascular sequelae or need for adjunct therapies were recorded for consecutive visits after meeting vision criteria (maximum of 16 visits). In the central retinal vein occlusion (CRVO) cohort, univariate and multivariate analyses were performed to identify factors predictive of outcomes, and the incidence of sequelae was studied with survival analysis. MAIN OUTCOME MEASURES: Change in approximate Early Treatment Diabetic Retinopathy Study (ETDRS) letter score at 6 and 12 months. RESULTS: The CRVO patients (n = 39) gained a median of 20 letters relative to baseline at both 6 and 12 months and showed a change in central subfield thickness (CST) of -504.1 µm and -552.3 µm, respectively. Branch RVO and hemiretinal vein occlusion patients (n = 13) gained a median of +45 and +57.5 letters at 6 and 12 months, respectively, and showed reductions of 299.6 µm and 355.2 µm of CST on SD OCT. For CRVO patients, more time from symptom onset to first injection predicted less optimistic letter gains in unadjusted and adjusted models (P < 0.0001 for all measures). A delay from symptom onset to first injection of 30 days or more predicted higher incidence of both neovascular (hazard ratio, 11.036; 95% confidence interval [CI], 1.807-67.393) and total (hazard ratio, 11.425, 95% CI, 1.940-67.300) events. CONCLUSIONS: Patients with RVO demonstrating poor initial visual acuity showed visual and anatomic benefit with anti-VEGF therapy, most often observed shortly after initiation of treatment. In CRVO patients, even minor delays between symptom onset and first injection led to less optimistic vision gains and were associated with higher incidence of negative sequelae.

A novel phenotype of torpedo maculopathy on spectral-domain optical coherence tomography.

PURPOSE: To present a new phenotype of torpedo maculopathy on spectral domain optical coherence tomography imaging (SD-OCT). OBSERVATIONS: A 31-year-old female presented with a multi-partite yellowish lesion in the macula of her left eye, with a central fovea-involving component and a temporal tail-like component. The lesion showed mixed hyper- and hypoautofluorescence on fundus autofluorescence imaging. The fovea-involving component exhibited disruption of ellipsoid zone without outer-retinal cavitation on SD-OCT, consistent with the prior-described type 1 OCT morphology. The temporal tail showed subtle inner choroidal excavation with preservation of the ellipsoid zone and outer-retinal structures. CONCLUSIONS: Inner choroidal excavation with preservation of the overlying outer-retinal structures represents a novel morphological phenotype on SD-OCT in torpedo maculopathy. This case demonstrates that distinct morphological subtypes may co-exist in different regions of the same torpedo maculopathy lesion.

Quantifying the Rate of Ellipsoid Zone Loss in Stargardt Disease.

PURPOSE: To determine a reliable method of using the ellipsoid zone (EZ) on optical coherence tomography (OCT) to track disease progression in Stardgardt disease (STGD). DESIGN: Retrospective reliability study. METHODS: STGD patients with genetically confirmed ABCA4 gene mutations seen at the Wilmer Eye Institute with follow-up visits separated by at least 12 months were identified. Spectral-domain optical coherence tomography (SD-OCT) macula volume scans centered at the fovea and fundus autofluorescence (FAF) images were obtained. The area of EZ loss was calculated from the SD-OCT and the area of retinal pigment epithelium (RPE) loss from the FAF. Scans were reanalyzed by the primary grader to assess intragrader reliability, and reanalyzed by a second grader to assess intergrader reliability. RESULTS: Sixteen STGD patients (total of 31 eyes) were followed for a mean of 2 years (range 1-4.7 years). The mean rate of EZ loss, 0.31 ± 0.31 mm2/year, was similar to the average rate of RPE loss, 0.33 ± 0.38 mm2/year. The average area of EZ loss at the initial examination, 4.18 ± 1.91 mm2, was larger than the initial area of RPE loss, 2.25 ± 1.66 mm2 (P < .01). The absolute difference of the area of EZ loss on test-retest for the first grader was 0.12 ± 0.10 mm2, and between graders 0.21 ± 0.21 mm2. The intraclass correlation (ICC) of both intragrader and intergrader reliability for EZ loss was excellent at 0.99. CONCLUSIONS: Tracking the area of EZ loss on SD-OCT macular volume scans longitudinally is a reliable way of monitoring disease progression in STGD. This could be used as a sensitive anatomic outcome measure in clinical trials related to STGD.

Genome-Wide Scleral Micro- and Messenger-RNA Regulation During Myopia Development in the Mouse.

PURPOSE: MicroRNA (miRNAs) have been previously implicated in scleral remodeling in normal eye growth. They have the potential to be therapeutic targets for prevention/retardation of exaggerated eye growth in myopia by modulating scleral matrix remodeling. To explore this potential, genome-wide miRNA and messenger RNA (mRNA) scleral profiles in myopic and control eyes from mice were studied. METHODS: C57BL/6J mice (n = 7; P28) reared under a 12L:12D cycle were form-deprived (FD) unilaterally for 2 weeks. Refractive error and axial length changes were measured using photorefraction and 1310-nm spectral-domain optical coherence tomography, respectively. Scleral RNA samples from FD and fellow control eyes were processed for microarray assay. Statistical analyses were performed using National Institute of Aging array analysis tool; group comparisons were made using ANOVA, and gene ontologies were identified using software available on the Web. Findings were confirmed using quantitative PCR in a separate group of mice (n = 7). RESULTS: Form-deprived eyes showed myopic shifts in refractive error (-2.02 ± 0.47 D; P < 0.01). Comparison of the scleral RNA profiles of test eyes with those of control eyes revealed 54 differentially expressed miRNAs and 261 mRNAs fold-change >1.25 (maximum fold change = 1.63 and 2.7 for miRNAs and mRNAs, respectively) (P < 0.05; minimum, P = 0.0001). Significant ontologies showing gene over-representation (P < 0.05) included intermediate filament organization, scaffold protein binding, detection of stimuli, calcium ion, G protein, and phototransduction. Significant differential expression of Let-7a and miR-16-2, and Smok4a, Prph2, and Gnat1 were confirmed. CONCLUSIONS: Scleral mi- and mRNAs showed differential expression linked to myopia, supporting the involvement of miRNAs in eye growth regulation. The observed general trend of relatively small fold-changes suggests a tightly controlled, regulatory mechanism for scleral gene expression.