Impending anterior ischemic optic neuropathy with elements of retinal vein occlusion in a patient on interferon for polycythemia vera.

We describe the course and likely pathophysiology of impending anterior ischemic optic neuropathy (AION) and retinal vein occlusion in a 56-year-old man with polycythemia vera managed with interferon alpha for 2 years. Our patient presented with decreased vision, scintillating scotomata, and floaters. Fundus examination findings and results of a fluorescein angiogram led to the diagnosis of impending AION and retinal vein occlusion. Considering that both polycythemia vera and interferon have possible influences on vascular occlusion and optic disc edema, we stopped interferon treatment and immediately attempted to treat the polycythemia vera empirically with pentoxifylline and any interferon-associated inflammation with prednisone. Our patient experienced complete resolution of fundus abnormalities and return of normal vision within 3 weeks, which may be attributed to our successful treatment of both etiologies. Thus, further study is warranted to elucidate the treatment of both polycythemia vera and interferon-induced impending AION

Three-dimensional computer-automated threshold Amsler grid test

We describe a novel method for testing a visual field that employs a computer monitor with displays of varying contrast that permits unprecedented resolution and characterization of the structure of scotomas in three dimensions. Patients are placed in front of a touch-sensitive computer screen at a fixed distance. With one eye covered, they focus on a central fixation marker and trace with their finger the areas on an Amsler grid that are missing from their field of vision. Increasing degrees of contrast of the Amsler grid are simulated by repeating the test at different gray-scale levels. The results are recorded and then displayed as topographical contour rings by the computer test program. The results can also be rendered as an immediate 3-D depiction of the central hill-of-vision. Several clinical pilot studies have been conducted at the Doheny Eye Institute and more than 200 patients have been examined with this system so far. Conditions such as optic neuritis, anterior ischemic optic neuropathy (AION), age-related macular degeneration (AMD), glaucoma, and ocular hypertension have been successfully assessed by this test. Each condition provides unique patterns that are most evident in 3-D. The 3-D computer-automated threshold Amsler grid test is an innovative and noninvasive visual field test. It provides several advantages over state-of-the-art standard automated perimetry, including: (1) additional information through 3-D depiction of scotomas, such as location, extent, slope, depth, and shape; (2) high angular resolution (1 deg compared with typically 6 deg); (3) a simple test setup (merely a touch-sensitive computer monitor and the test software); (4) excellent patient compliance (spending 4 to 5 min per eye). In light of its promising initial tests, the 3-D visual field test appears to have the potential for the early detection and monitoring of various diseases over time

Optical Coherence Tomography Angiography of the Optic Disc; an Overview.

Different diseases of the optic disc may be caused by or lead to abnormal vasculature at the optic nerve head. Optical coherence tomography angiography (OCTA) is a novel technology that provides high resolution mapping of the retinal and optic disc vessels. Recent studies have shown the ability of OCTA to visualize vascular abnormalities in different optic neuropathies. In addition, quantified OCTA measurements were found promising for differentiating optic neuropathies from healthy eyes

A Female Patient with Down Syndrome and Low-Penetrance Leber's Hereditary Optic Neuropathy.

We present the case of a 19-year-old female with a history of Down syndrome (DS) who was referred to our neuro-ophthalmology clinic for evaluation of Leber's hereditary optic neuropathy (LHON). The patient's family history was significant for a known G11778A mutation in a maternal relative, consistent with LHON. The patient was also positive for the G11778A mutation; however, the genotype demonstrated low penetrance in the pedigree, with only 1 out of 10 adult male offspring showing signs or symptoms of the disease. Mitochondrial mutations implicated in LHON have been shown to impair complex I of the electron transport chain and thereby reducing the effective generation of adenosine triphosphate and increasing the production of toxic reactive oxygen species. Although the partial or complete triplicate of chromosome 21 constitutes the etiology of DS, some of the pleiotropic phenotypes of the syndrome have been attributed to oxidative stress and mitochondrial dysfunction. Given the low penetrance of the mutation and the patient's sex, this case illustrates the possibility that the mitochondrial mutation demonstrated increased penetrance due to pre-existing mitochondrial dysfunction related to DS

Medical management of hereditary optic neuropathies.

Hereditary optic neuropathies are diseases affecting the optic nerve. The most common are mitochondrial hereditary optic neuropathies, i.e., the maternally inherited Leber's hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA). They both share a mitochondrial pathogenesis that leads to the selective loss of retinal ganglion cells and axons, in particular of the papillo-macular bundle. Typically, LHON is characterized by an acute/subacute loss of central vision associated with impairment of color vision and swelling of retinal nerve fibers followed by optic atrophy. DOA, instead, is characterized by a childhood-onset and slowly progressive loss of central vision, worsening over the years, leading to optic atrophy. The diagnostic workup includes neuro-ophthalmologic evaluation and genetic testing of the three most common mitochondrial DNA mutations affecting complex I (11778/ND4, 3460/ND1, and 14484/ND6) for LHON and sequencing of the nuclear gene OPA1 for DOA. Therapeutic strategies are still limited including agents that bypass the complex I defect and exert an antioxidant effect (idebenone). Further strategies are aimed at stimulating compensatory mitochondrial biogenesis. Gene therapy is also a promising avenue that still needs to be validated

Clues from Crouzon: Insights into the potential role of growth factors in the pathogenesis of myelinated retinal nerve fibers.

PurposeWe present a case of bilateral extensive peripapillary myelinated retinal nerve fibers (MRNF) in an individual with Crouzon syndrome, an inherited form of craniosynostosis caused by overactivation of fibroblast growth factor receptor 2. As a secondary aim, we examine the utility of optical coherence tomography (OCT) angiography for visualization of peripapillary vasculature obscured by myelination on other imaging modalities.MethodsA 24-year-old woman with Crouzon syndrome was evaluated for suspected optic neuritis in the right eye.ResultsFunduscopic examination and photography revealed the incidental finding of bilateral extensive peripapillary MRNF. OCT angiography provided excellent visualization of peripapillary retinal vessels, which were partially obscured by myelination on other imaging modalities.ConclusionsThis association of Crouzon syndrome with bilateral peripapillary MRNF may lend insight into the developmental control of optic nerve myelination, the pathogenesis of MRNF, and the potential role of growth factors in these processes. Further, OCT angiography allowed for excellent blood vessel visualization in this case of MRNF

Distinguishing wet from dry age-related macular degeneration using three-dimensional computer-automated threshold Amsler grid testing

Background/aims: With the increased efficacy of current therapy for wet age-related macular degeneration (AMD), better ways to detect wet AMD are needed. This study was designed to test the ability of three-dimensional contrast threshold Amsler grid (3D-CTAG) testing to distinguish wet AMD from dry AMD. Methods: Conventional paper Amsler grid and 3D-CTAG tests were performed in 90 eyes: 63 with AMD (34 dry, 29 wet) and 27 controls. Qualitative comparisons were based upon the three-dimensional shapes of central visual field (VF) defects. Quantitative analyses considered the number and volume of the three-dimensional defects. Results: 25/34 (74%) dry AMD and 6/29 (21%) wet AMD eyes had no distortions on paper Amsler grid. Of these, 5/25 (20%) dry and 6/6 (100%) wet (p=0.03) AMD eyes exhibited central VF defects with 3D-CTAG. Wet AMD displayed stepped defects in 16/28 (57%) eyes, compared with only 2/34 (6%) of dry AMD eyes (p=0.002). All three volumetric indices of VF defects were two- to four-fold greater in wet than dry AMD (p<0.006). 3D-CTAG had 83.9% positive and 90.6% negative predictive values for wet AMD. Conclusions: 3D-CTAG has a higher likelihood of detecting central VF defects than conventional Amsler grid, especially in wet AMD. Wet AMD can be distinguished from dry AMD by qualitative and quantitative 3D-CTAG criteria. Thus, 3D-CTAG may be useful in screening for wet AMD, quantitating disease severity, and providing a quantitative outcome measure of therapy

Angioarchitectural evolution of clival dural arteriovenous fistulas in two patients.

Dural arteriovenous fistulas (dAVFs) may present in a variety of ways, including as carotid-cavernous sinus fistulas. The ophthalmologic sequelae of carotid-cavernous sinus fistulas are known and recognizable, but less commonly seen is the rare clival fistula. Clival dAVFs may have a variety of potential anatomical configurations but are defined by the involvement of the venous plexus just overlying the bony clivus. Here we present two cases of clival dAVFs that most likely evolved from carotid-cavernous sinus fistulas