Boucher-Neuhauser Syndrome: Chorioretinal Changes in a Single Case Over Time.

PURPOSE: To describe chorioretinal changes in a single case of Boucher-Neuhauser Syndrome (BNHS) over 45 years of follow-up. Methods: Retrospective chart review was performed. Color fundus photography from 1977 to 2003 was obtained and digitized. Current fundus photography was obtained with widefield imaging. High-resolution spectral-domain optical coherence tomography (OCT) was performed. Genetic analysis was performed using an inherited retinal disorders panel. Results: Fundus examination demonstrated central chorioretinal atrophy with sclerotic choroidal vessels. Short posterior ciliary arteries became more prominent and tortuous over time. Mid-peripheral atrophy extends to the equator and demonstrates a scalloped pattern with islands of atrophy intervening with areas of normal retina. The far periphery remained minimally affected. High-resolution OCT demonstrated outer retinal atrophy and choriocapillaris loss. Genetic testing showed a homozygous variant for PNPLA6 and a heterozygous variant for TYRP1. Conclusion: Chorioretinal changes in BNHS vary in onset and severity. It is important to diagnose this condition in order to begin timely management of visual and systemic sequelae.

Case series: Fundus autofluorescence abnormalities in a family of ocular albinism carriers.

SIGNIFICANCE: Carriers of ocular albinism demonstrate signs of retinal mosaicism with unique features on fundus autofluorescence testing, which differentiate this condition from other x-linked retinal disorders in carrier patients. Distinctive findings include a mud-splattered fundus with peripheral hyperpigmented streaks, which correlate with areas of hyperautofluorescence and hypoautofluorescence. PURPOSE: This is the first reported case series of a family that demonstrates diagnostic retinal and fundus autofluorescence abnormalities related to retinal mosaicism in three sisters who were unaware they were carriers of ocular albinism type 1. Multimodal imaging, electrodiagnostic testing, and genetic testing can be used to confirm the diagnosis and differentiate this clinical presentation from other sight-threatening hereditary retinal diseases. CASE REPORTS: Three sisters, aged 21, 17, and 13 years, were referred to determine the cause of abnormal retinal pigmentation. All presented with normal vision, and anterior segment examination was unremarkable without iris transillumination. They denied family history of ocular disease. Fundus examination of all three sisters revealed a mud-splattered pattern of pigmentation in the posterior pole and radial pigmentary streaks. Fundus autofluorescence showed a pattern of hyperautofluorescence and hypoautofluorescence corresponding to this pigmentary pattern. Spectral domain optical coherence tomography, electro-oculogram, and electroretinogram were normal in all three sisters. Genetic testing of their father, who was unaware of any disorder, tested positive for ocular albinism. CONCLUSIONS: Ocular albinism carriers have abnormal retinal pigmentation in a characteristic pattern. Fundus autofluorescence shows a correlative pattern that can confirm carrier status of ocular albinism in individuals unaware of their status and rule out other retinal degenerations.

Case Series: Multimodal Imaging Reveals the Spectrum of Pattern Dystrophies of the Retinal Pigment Epithelium.

SIGNIFICANCE: Pattern dystrophies of the retinal pigment epithelium, often misdiagnosed as other macular conditions, were once considered a rare retinal disease. However, an increasing number of cases have recently been discovered owing to advancements in multimodal imaging and increased awareness of the condition. PURPOSE: The purposes of this study were to increase awareness of pattern dystrophies and to review how to accurately diagnose and manage pattern dystrophies by understanding their presentation on fundus autofluorescence, optical coherence tomography, and electrodiagnostic testing. CASE SERIES: Three cases of patients diagnosed as having pattern dystrophies are reported. In case 1, fundus autofluorescence, optical coherence tomography, and electrodiagnostic testing aid in diagnosing multifocal pattern dystrophy. The same tools are used to diagnose adult-onset foveomacular vitelliform dystrophy in case 2 and reticular pattern dystrophy in case 3. CONCLUSIONS: Fundus autofluorescence, optical coherence tomography, and electrodiagnostic testing facilitate the proper diagnosis of patients with pattern dystrophies. With increased awareness of pattern dystrophies and increased use of multimodal imaging, pattern dystrophies will likely no longer be considered rare.

A proposed mechanism influencing structural patterns in X-linked retinoschisis and stellate nonhereditary idiopathic foveomacular retinoschisis.

OBJECTIVE: To explore the structural differences between X-linked retinoschisis (XLR) and stellate nonhereditary idiopathic foveomacular retinoschisis (SNIFR) using swept-source optical coherence tomography angiography (SS-OCTA). METHODS: A case series of two patients, a 9-year-old male with XLR and a 58-year-old woman with SNIFR were imaged with swept-source optical coherence tomography angiography (SS-OCTA; PLEX Elite 900, Carl Zeiss Meditec, Inc, Dublin, CA). Automated segmentation was manually adjusted to include the areas of retinoschisis within en face flow and structural slabs. The flow data were binarized using ImageJ 1.51s (Wayne Rasband, National Institutes of Health, USA, http://imagej.nih.gov.ij ) and superimposed onto the structural slab. RESULTS: In the eye with XLR, OCTA flow data superimposed on the structural slab demonstrated flow signal within numerous bridging structures connecting the inner and outer plexiform layers containing the intermediate (ICP) and deep (DCP) capillary plexuses. In contrast, the same technique applied to the eye with SNIFR demonstrated an absence of flow signal in the cystic retinal spaces within Henle's fiber layer. CONCLUSIONS: The vascular pattern of bridging vessels between the ICP and DCP is closely related to the structural "retinoschisis" pattern of XLR and appears to be structurally different from that seen in SNIFR. Moreover, the connecting vessels appear to be highly represented and regularly distributed, thereby supporting a serial arrangement of the retinal capillary plexuses within the perifoveal macula.

A review of mitochondrial optic neuropathies: from inherited to acquired forms / Revisión de las neuropatías ópticas mitocondriales: de las formas hereditarias a las adquiridas

In recent years, the term mitochondrial optic neuropathy (MON) has increasingly been used within the literature to describe a group of optic neuropathies that exhibit mitochondrial dysfunction in retinal ganglion cells (RGCs). Interestingly, MONs include genetic aetiologies, such as Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), as well as acquired aetiologies resulting from drugs, nutritional deficiencies, and mixed aetiologies. Regardless of an inherited or acquired cause, patients exhibit the same clinical manifestations with selective loss of the RGCs due to mitochondrial dysfunction. Various novel therapies are being explored to reverse or limit damage to the RGCs. Here we review the pathophysiology, clinical manifestations, differential diagnosis, current treatment, and promising therapeutic targets of MON (AU)

En los últimos años, se ha incrementado el uso en la literatura del término neuropatía óptica mitocondrial (MON), para describir un grupo de neuropatías ópticas que presentan una disfunción mitocondrial en las células ganglionares de la retina (RGC). De manera interesante, las MON incluyen etiologías genéticas, tales como Neuropatía Óptica Hereditaria de Leber (LHON) y Atrofia Óptica Dominante (DOA), así como etiologías adquiridas derivadas del consumo de drogas, deficiencias nutricionales y etiologías mixtas. Independientemente de que la causa sea hereditaria o adquirida, los pacientes presentan las mismas manifestaciones clínicas, con pérdida selectiva de RGCs debido a la disfunción mitocondrial. Se están explorando diversas terapias novedosas para revertir o limitar el daño a las RGC. En este documento revisamos la patofisiología, las manifestaciones clínicas, los diagnósticos diferenciales, el tratamiento actual y los prometedores objetivos terapéuticos de las MON (AU)

A Review of Mitochondrial Optic Neuropathies: From Inherited to Acquired Forms.

In recent years, the term mitochondrial optic neuropathy (MON) has increasingly been used within the literature to describe a group of optic neuropathies that exhibit mitochondrial dysfunction in retinal ganglion cells (RGCs). Interestingly, MONs include genetic aetiologies, such as Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), as well as acquired aetiologies resulting from drugs, nutritional deficiencies, and mixed aetiologies. Regardless of an inherited or acquired cause, patients exhibit the same clinical manifestations with selective loss of the RGCs due to mitochondrial dysfunction. Various novel therapies are being explored to reverse or limit damage to the RGCs. Here we review the pathophysiology, clinical manifestations, differential diagnosis, current treatment, and promising therapeutic targets of MON.

OCT in a Myelinated Retinal Nerve Fiber Syndrome with Reduced Vision.

PURPOSE: The prognosis of success with vision therapy in refractive "amblyopia" associated with the syndrome of myelinated nerve fibers (MRNF), optic disc hypoplasia, and myopia is reported to be poorer than that of anisomyopic amblyopia without these features. The reason for the poorer prognosis has not been well understood. The purpose of this study was to perform spectral domain (SD) ocular coherence tomography (OCT) to determine if there is a structural etiology that may explain the poorer prognosis. CASE REPORTS: Case 1 was a 12-year-old male patient with anisometropic "amblyopia" in the right eye, MRNF denser superiorly, a hypoplastic disc, and a myopic fundus with a flat intact macula. The OCT demonstrated an attenuated photoreceptor integrity line (PIL) in the macula. Case 2 was a 10-year-old male patient with a constant left esotropia, MRNF denser superiorly, a hypoplastic disc, and a myopic fundus with a flat intact macula. The OCT demonstrated an absent PIL. Case 3 was a 58-year-old female patient with a history of diabetic retinopathy OU, long-standing reduced vision in the right eye, MRNF denser superiorly, optic nerve hypoplasia, and a myopic fundus with an intact macula. The OCT demonstrated an absent PIL in the macula. CONCLUSIONS: This case series identifies three patients with the syndrome of MRNF, optic nerve hypoplasia, and anisomyopia in one eye with reduced vision and reports OCT findings using SD-OCT systems. All three patients demonstrated an absence or attenuation of the photoreceptor integrity line (PIL) in the macula in the affected eye. To our knowledge, there is no known association between this syndrome and abnormality of the PIL reported in the literature. Patients with this syndrome may have a guarded prognosis in the success of vision therapy.

Visual acuity recovery in a case of idiopathic retinal vasculitis aneurysms and neuroretinitis.

PURPOSE: To describe the visual recovery after intravitreal injections of the antivascular endothelial growth factor, bevacizumab, in a case of vaso obliteration from idiopathic retinal vasculitis, aneurysm, and neuroretinitis (IRVAN). The name IRVAN was given to the condition to highlight the key findings present in the disease. IRVAN is a severe, sight threatening condition that can lead to peripheral capillary non-perfusion and vision loss from the ischemic sequelae of vascular occlusion. Panretinal photocoagulation (PRP) is the current standard of care for IRVAN but visual outcome is poor if PRP is initiated after neovascularization develops. Intravitreal bevacizumab has success at treating neovascularization from other ischemic retinopathies and inflammatory retinal conditions that have similar characteristics to IRVAN. CASE REPORT: This case report describes a patient with decreased vision in the OS. The patient presented with best-corrected visual acuity of 20/20 in the OD and count fingers at 4 ft in the OS. Evaluation revealed findings consistent with an advanced stage of IRVAN. Anterior and posterior neovascularization had developed from extensive capillary non-perfusion in both retinas. A dense vitreous hemorrhage blocked vision OS. Bilateral intravitreal injections of bevacizumab and extensive PRP were given in the area of retinal ischemia for treatment. After 4 months, the patient's vision had improved from count fingers in the OS to 20/40. CONCLUSIONS: IRVAN has favorable outcomes when treated with a combination of PRP and intravitreal injections of antivascular endothelial growth factor. This case demonstrates the effectiveness of this combination treatment in a case of IRVAN with both posterior and anterior neovascularization.

Bilateral Coats' response in a female patient leads to diagnosis of facioscapulohumeral muscular dystrophy.

BACKGROUND: Facioscapulohumeral dystrophy (FSHD) is a rare autosomal dominant muscle disease that affects about 5 in 100,000 individuals. Retinal vascular changes that mimic Coats' disease have been described in previously diagnosed FSHD. We report a diagnosis of FSHD only after the detection of a rare bilateral Coats' response in a female patient. CASE REPORT: A 39-year-old asymptomatic black woman presented for a second opinion of a lesion previously diagnosed as an isolated hemangioma in the left temporal retina. She had no relevant family or personal health history. She was not born prematurely, did not show evidence of autoimmune disease, and had a normal hemoglobin electrophoresis. Examination found an exudative mass in the left temporal retina and subtle telangiectatic vessels in the right temporal retina. Optomap® (Optos®, Dunfermline, Scotland) fluorescein angiography found multiple areas of capillary drop-out, arborization, and telangiectatic microaneurysms in both eyes (left eye greater than right eye). Genetic testing results were positive for a deletion of tandemly repeated DNA (D4Z4 repeats) in chromosome 4q35 consistent with a diagnosis of FSHD. CONCLUSION: A prior diagnosis of FSHD alerts the clinician to look for a Coats' response in the retina. However, bilateral Coats' disease in a female should alert the clinician to test for FSHD.

Choroidal neovascularization in a young, healthy eye after LASIK.

BACKGROUND: Choroidal neovascularization (CNV) is associated with age-related macular degeneration (AMD), degenerative myopia, angioid streaks, presumed ocular histoplasmosis syndrome, and numerous other ocular and systemic conditions. Idiopathic CNV is also a common form of the condition. However, CNV has rarely been noted after laser-assisted in situ keratomileusis (LASIK) and a cause-and-effect relationship has not been found. A case of CNV after uneventful LASIK is reported here, along with a literature review of previously reported cases and suggested pathophysiology. A link between LASIK and CNV is sought. METHODS: A case report of CNV in a young, healthy eye after uneventful LASIK is presented. Review of the pertinent literature reporting a relationship between LASIK and CNV was conducted through 2007, and few studies are reported after 2005. CONCLUSION: To date, there is anecdotal evidence of CNV after LASIK. The incidence from prior reports ranges from 0.003% to 0.33%. However, a causal link cannot be disregarded and merits further study. Each patient undergoing LASIK warrants a thorough preoperative dilated fundus examination, including a thorough examination of the macula. This occurrence, albeit rare, should be considered for inclusion in the refractive surgery consent form.

A Thr17Met mutation is associated with an unusual retinochoroidopathy in an autosomal dominant pedigree.

PURPOSE: To report the results of molecular genetic analysis for a proband with unusual regionalized retinochoroidopathy in an autosomal dominant pedigree originally reported as a previously undescribed condition. METHODS: Genomic DNA was obtained from the proband's leukocytes and was analyzed by Carver Laboratories at the University of Iowa (Iowa City) specifically to look for variants in genes associated with autosomal dominant retinitis pigmentosa. RESULTS: A probable high-penetrance disease-causing sequence variation in the rhodopsin gene, a heterozygous cytosine-to-thymine ACG>ATG nucleotide substitution resulting in a threonine to methionine (Thr17Met) amino acid change, was detected. This variant is associated with autosomal dominant retinitis pigmentosa. CONCLUSION: Findings of molecular genetics analysis of this unusual regionalized retinochoroidopathy support the diagnosis of a mild, delimited form of autosomal dominant retinitis pigmentosa.

Comparison of an automated confrontation testing device versus finger counting in the detection of field loss.

PURPOSE: The aim of this study was to compare an automated confrontation visual field testing (ACV) device with traditional finger-counting confrontation visual field testing (FCV). METHODS: Forty-five eyes of 45 subjects with glaucoma, 5 eyes of 5 subjects with neurologic disease and 15 eyes of 15 normal subjects (age matched to the subjects with glaucoma by frequency) were tested on both ACV and FCV. All subjects with glaucoma and neurologic disease had visual field loss on white-on-white Humphrey perimetry (HVF). The FCV was performed in 8 meridians in a normally lighted room, whereas ACV was performed in a darkened room. The ACV device consisted of a black rectangular box with 4 1.0-mm red light-emitting diodes at each corner and a fixation hole at the center. Four automated randomized presentations were presented, and the subject was asked to identify the number of red lights seen (from 1 to 4). Any point missed on any of the presentations on either test was recorded as a failure. RESULTS: All normal subjects passed both tests. FCV detected field loss in 33.0% of glaucomatous eyes, whereas ACV detected field loss in 58% of glaucomatous eyes (P < 0.001). Subjects with glaucoma who passed FCV but failed ACV had an average mean deviation of -7.77 dB on HVF, compared with subjects who failed both FCV and ACV, who had an average mean deviation of -19.74 dB on HVF (P < 0.001). All subjects with absolute visual field loss because of advanced glaucoma or neurologic disease failed both tests. No subject who passed ACV failed FCV. CONCLUSIONS: Gross confrontation visual field testing using an automated testing device has a greater sensitivity in the detection of moderate visual field loss than finger counting confrontation visual fields.

Autosomal dominant pericentral retinochoroidal atrophy.

PURPOSE: To describe a family pedigree with a newly described hereditary retinal disease. METHODS: Five family members were examined, and a fifth deceased family member was identified through review of old medical records. RESULTS: Five individuals had annular or arcuate pericentral areas of retinal (younger members) or choroidal (older members) atrophy and spared maculae with good visual acuity and normal retinal periphery. Two of the four examined affected family members were symptomatic only for field loss; the other two were asymptomatic. No nyctalopia was reported by any affected individual. Fluorescein angiography revealed hyperfluorescence in the affected areas in the family members with retinal atrophy and hypofluorescence in affected areas in family members with choroidal atrophy. Visual field scotomas were dense and corresponded to the areas of retinal and/or choroidal atrophy. Full-field electroretinograms were normal for two family members and were reduced for one family member with the most advanced retinal and choroidal changes. The scotopic response was only mildly reduced in the fourth examined family member. CONCLUSIONS: We believe that we have identified a pedigree with a previously undescribed autosomal dominant hereditary retinal disease characterized by arcuate retinal and retinochoroidal atrophy and normal visual acuity.

Glaucoma without cupping.

BACKGROUND: Although glaucoma can exist with normal intraocular pressures (IOPs), clinicians still rely on the presence of a large cup to "flag" suspects, regardless of IOP, whereas a small cup at the same pressure level is often ignored. High-tech instruments offer a new dimension of evaluation in the objective assessment of structure when subjective tests of function and/or ophthalmoscopic observations are equivocal. CASE REPORTS: Thirteen cases are presented and show evidence of glaucoma based on glaucomatous visual-field defects, often with steadily rising intraocular pressures and retinal nerve fiber layer loss. Surprisingly, these patients maintained small C/D ratios. Accordingly, ophthalmoscopy and/or disk topography classified these disks as normal. CONCLUSIONS: Although unrecognized in virtually the entire world's ophthalmic literature, normal cup glaucoma is a real clinical entity. At least half the normal cup glaucoma cases presented herein have disk drusen (obvious, subtle, or occult), while others are highly myopic and/or have documented IOP spikes. Several of the cases defy classification and explanation at the present time.

Optic disk evaluation and utility of high-tech devices in the assessment of glaucoma.

BACKGROUND: Every clinician has at one time or another examined a patient who was misdiagnosed as having glaucoma or whose diagnosis of glaucoma was missed. Although glaucoma can exist with normal intraocular pressures, clinicians often rely on the presence of visual-field defects and the degree of optic disk cupping to direct care. However, assessment of cupping is but one small part of optic disk evaluation in glaucoma, and other features of the optic nerve head and retinal nerve fiber layer must be closely inspected to help diagnose borderline cases. In addition, glaucoma can exist without visual-field loss. High-tech devices offer an added dimension in the objective assessment of structure when subjective tests of function and/or ophthalmoscopic observations are equivocal. METHODS: This article details the various parameters of optic disk and retinal nerve fiber layer evaluation and their significance in the assessment of glaucoma. In addition, the role of four high-tech devices is evaluated for their utility in the assessment and progression of glaucomatous damage. CONCLUSIONS: When one attempts to classify a patient as having glaucoma, the degree of cupping and the presence or absence of visual field loss can be misleading. Prior to definitive diagnosis, a thorough evaluation of the optic disk and retinal nerve fiber layer, and appropriate use of high-tech devices, should help reduce the under-diagnosis and overdiagnosis of this disease.