The diagnostic accuracy of photopic negative responses evoked by broadband and chromatic stimuli in a clinically heterogeneous population.

PURPOSE: To compare the diagnostic accuracy of the photopic negative response (PhNR) elicited by red-blue (RB) and white-white (WW) stimuli, for detection of retinal ganglion cell (RGC) dysfunction in a heterogeneous clinical cohort. METHODS: Adults referred for electrophysiological investigations were recruited consecutively for this single-centre, prospective, paired diagnostic accuracy study. PhNRs were recorded to red flashes (1.5 cd·s·m-2) on a blue background (10 cd·m-2) and to white flashes on a white background (the latter being the ISCEV standard LA 3 stimulus). PhNR results were compared with a reference test battery assessing RGC/optic nerve structure and function including optical coherence tomography (OCT) retinal nerve fibre layer thickness and mean RGC volume measurements, fundus photography, pattern electroretinography and visual evoked potentials. Primary outcome measures were differences in sensitivity and specificity of the two PhNR methods. RESULTS: Two hundred and forty-three participants were initially enrolled, with 200 (median age 54; range 18-95; female 65%) meeting inclusion criteria. Sensitivity was 53% (95% confidence intervals [CI] 39% to 68%) and 62% (95% CI 48% to 76%), for WW and RB PhNRs, respectively. Specificity was 80% (95% CI 74% to 86%) and 78% (95% CI 72% to 85%), respectively. There was a statistically significant difference between sensitivities (p = 0.046) but not specificities (p = 0.08) of the two methods. Receiver operator characteristic (ROC) area under the curve (AUC) values were 0.73 for WW and 0.74 for RB PhNRs. CONCLUSION: PhNRs to red flashes on a blue background may be more sensitive than white-on-white stimuli, but there is no significant difference between specificities. This study highlights the value and potential convenience of using white-on-white stimuli, already used widely for routine ERG assessment.

Toxic optic neuropathy associated with lamotrigine and levetiracetam dual therapy.

We report the case of an early adolescent male on lamotrigine and levetiracetam therapy with a 1-month history of progressive, bilateral, painless visual loss which resolved on cessation of lamotrigine. To our knowledge, we present the first case of lamotrigine and levetiracetam dual therapy associated with toxic optic neuropathy, supported by electrophysiology and optical coherence tomography (OCT) changes. Electrophysiology findings were consistent with retinal ganglion cell dysfunction, with bilateral optic nerve involvement. Macula OCT showed mild retinal ganglion cell loss in all inner quadrants bilaterally. This case highlights the importance of asking patients with epilepsy treated with lamotrigine and levetiracetam about visual problems and considering early dose reduction or cessation of treatment.

Electrodiagnostic tests of the visual pathway and applications in neuro-ophthalmology.

This article describes the main visual electrodiagnostic tests relevant to neuro-ophthalmology practice, including the visual evoked potential (VEP), and the full-field, pattern and multifocal electroretinograms (ffERG; PERG; mfERG). The principles of electrophysiological interpretation are illustrated with reference to acquired and inherited optic neuropathies, and retinal disorders that may masquerade as optic neuropathy, including ffERG and PERG findings in cone and macular dystrophies, paraneoplastic and vascular retinopathies. Complementary VEP and PERG recordings are illustrated in demyelinating, ischaemic, nutritional (B12), and toxic (mercury, cobalt, and ethambutol-related) optic neuropathies and inherited disorders affecting mitochondrial function such as Leber hereditary optic neuropathy and dominant optic atrophy. The value of comprehensive electrophysiological phenotyping in syndromic diseases is highlighted in cases of SSBP1-related disease and ROSAH (Retinal dystrophy, Optic nerve oedema, Splenomegaly, Anhidrosis and Headache). The review highlights the value of different electrophysiological techniques, for the purposes of differential diagnosis and objective functional phenotyping.

Shifting mirrors: adaptive changes in retinal reflections to winter darkness in Arctic reindeer.

Arctic reindeer experience extreme changes in environmental light from continuous summer daylight to continuous winter darkness. Here, we show that they may have a unique mechanism to cope with winter darkness by changing the wavelength reflection from their tapetum lucidum (TL). In summer, it is golden with most light reflected back directly through the retina, whereas in winter it is deep blue with less light reflected out of the eye. The blue reflection in winter is associated with significantly increased retinal sensitivity compared with summer animals. The wavelength of reflection depends on TL collagen spacing, with reduced spacing resulting in shorter wavelengths, which we confirmed in summer and winter animals. Winter animals have significantly increased intra-ocular pressure, probably produced by permanent pupil dilation blocking ocular drainage. This may explain the collagen compression. The resulting shift to a blue reflection may scatter light through photoreceptors rather than directly reflecting it, resulting in elevated retinal sensitivity via increased photon capture. This is, to our knowledge, the first description of a retinal structural adaptation to seasonal changes in environmental light. Increased sensitivity occurs at the cost of reduced acuity, but may be an important adaptation in reindeer to detect moving predators in the dark Arctic winter.

A phenotype-genotype correlation study of X-linked retinoschisis.

PURPOSE: To compare the clinical phenotype and detailed electroretinographic parameters in X-linked retinoschisis (XLRS). DESIGN: Retrospective, comparative study. PARTICIPANTS: Fifty-seven patients (aged 1-67 years) with molecularly confirmed XLRS were clinically ascertained. METHODS: Pattern electroretinography (PERG) and full-field electroretinography (ERG), incorporating international standard recordings, were performed in 44 cases. Thirteen patients, mostly pediatric, were tested using a simplified ERG protocol. On-Off and S-cone ERGs were performed in most adults. Fundus autofluorescence (FAF) imaging and optical coherence tomography (OCT) were available in 17 and 21 cases, respectively. MAIN OUTCOME MEASURES: The clinical and electrophysiologic data associated with different types of mutation in the RS1 gene. RESULTS: Forty-three patients had missense changes (group A), and 14 patients had nonsense, splice-site, or frame-shifting mutations in the RS1 gene (group B). The mean best-corrected visual acuity was better in group A than in group B (0.34 and 0.21, respectively). Fundus examination revealed foveal schisis in approximately half of both groups. The bright-flash dark-adapted (DA) ERG (11.0 candela.sec.m(-2)) waveform was electronegative in 62% of group A eyes and 100% of group B eyes. The photopic 30-Hz flicker ERG was delayed in all group B eyes and all except 6 group A eyes. On-Off ERG b-waves were subnormal in 39% of group A and 89% of group B eyes; d-waves were delayed in 14 eyes (group A = 10, group B = 4). S-cone ERGs were abnormal in 50% of both groups. The PERG was abnormal in 88% of group A and 100% of group B eyes. A spoke-wheel pattern of high and low intensity was the most common FAF abnormality observed. The OCT showed intraretinal schitic cavities in the majority of eyes. CONCLUSIONS: There is profound phenotypic variability in patients with XLRS. Most patients have DA bright-flash ERGs with a low b:a ratio in keeping with inner retinal dysfunction. Generalized cone system dysfunction is common and associated with an abnormal On-response and less frequent additional Off-response involvement. Nonsense, splice-site, or frame-shifting mutations in RS1 consistently caused electronegative bright-flash ERG, delayed flicker response, and abnormal PERG; missense mutations result in a wider range of ERG abnormalities.

Ophthalmological Manifestations of Oculocutaneous and Ocular Albinism: Current Perspectives.

Albinism describes a heterogeneous group of genetically determined disorders characterized by disrupted synthesis of melanin and a range of developmental ocular abnormalities. The main ocular features common to both oculocutaneous albinism (OCA), and ocular albinism (OA) include reduced visual acuity, refractive errors, foveal hypoplasia, congenital nystagmus, iris and fundus hypopigmentation and visual pathway misrouting, but clinical signs vary and there is phenotypic overlap with other pathologies. This study reviews the prevalence, genetics and ocular manifestations of OCA and OA, including abnormal development of the optic chiasm. The role of visual electrophysiology in the detection of chiasmal dysfunction and visual pathway misrouting is emphasized, highlighting how age-associated changes in visual evoked potential (VEP) test results must be considered to enable accurate diagnosis, and illustrated further by the inclusion of novel VEP data in genetically confirmed cases. Differential diagnosis is considered in the context of suspected retinal and other disorders, including rare syndromes that may masquerade as albinism.

WFS1-Associated Optic Neuropathy: Genotype-Phenotype Correlations and Disease Progression.

OBJECTIVE: To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON). DESIGN: Multicenter cohort study. METHODS: The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmologic assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. MAIN OUTCOME MEASURES: WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile. RESULTS: Twenty-two recessive and 5 dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. CONCLUSIONS: WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe, vision and RGC loss compared with heterozygous variants. Abnormal cleftlike lamination of the OPL is a distinctive OCT feature that strongly points toward dominant WON.

Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways.

Developmental ocular malformations, including anophthalmia-microphthalmia (AM), are heterogeneous disorders with frequent sporadic or non-Mendelian inheritance. Recurrent interstitial deletions of 14q22-q23 have been associated with AM, sometimes with poly/syndactyly and hypopituitarism. We identify two further cases of AM (one with associated pituitary anomalies) with a 14q22-q23 deletion. Using a positional candidate gene approach, we analyzed the BMP4 (Bone Morphogenetic Protein-4) gene and identified a frameshift mutation (c.226del2, p.S76fs104X) that segregated with AM, retinal dystrophy, myopia, brain anomalies, and polydactyly in a family and a nonconservative missense mutation (c.278A-->G, p.E93G) in a highly conserved base in another family. MR imaging and tractography in the c.226del2 proband revealed a primary brain developmental disorder affecting thalamostriatal and callosal pathways, also present in the affected grandmother. Using in situ hybridization in human embryos, we demonstrate expression of BMP4 in optic vesicle, developing retina and lens, pituitary region, and digits strongly supporting BMP4 as a causative gene for AM, pituitary, and poly/syndactyly. Because BMP4 interacts with HH signaling genes in animals, we evaluated gene expression in human embryos and demonstrate cotemporal and cospatial expression of BMP4 and HH signaling genes. We also identified four cases, some of whom had retinal dystrophy, with "low-penetrant" mutations in both BMP4 and HH signaling genes: SHH (Sonic Hedgehog) or PTCH1 (Patched). We propose that BMP4 is a major gene for AM and/or retinal dystrophy and brain anomalies and may be a candidate gene for myopia and poly/syndactyly. Our finding of low-penetrant variants in BMP4 and HH signaling partners is suggestive of an interaction between the two pathways in humans.

Arctic reindeer extend their visual range into the ultraviolet.

The Arctic has extreme seasonal changes in light levels and is proportionally UV-rich because of scattering of the shorter wavelengths and their reflection from snow and ice. Here we show that the cornea and lens in Arctic reindeer do not block all UV and that the retina responds electrophysiologically to these wavelengths. Both rod and cone photoreceptors respond to UV at low-intensity stimulation. Retinal RNA extraction and in vitro opsin expression show that the response to UV is not mediated by a specific UV photoreceptor mechanism. Reindeer thus extend their visual range into the short wavelengths characteristic of the winter environment and periods of extended twilight present in spring and autumn. A specific advantage of this short-wavelength vision is the use of potential information caused by differential UV reflections known to occur in both Arctic vegetation and different types of snow. UV is normally highly damaging to the retina, resulting in photoreceptor degeneration. Because such damage appears not to occur in these animals, they may have evolved retinal mechanisms protecting against extreme UV exposure present in the daylight found in the snow-covered late winter environment.

Electroretinogram measures in a septuagenarian population.

This study reports electroretinogram (ERG) data in a septuagenarian population. Fifty healthy adults without diabetes or dementia aged 70-79 years underwent standardised electrophysiological testing incorporating current ISCEV Standards as baseline assessment for the OPAL (Older People And n-3 Long-chain polyunsaturated fatty acids) study. These data were compared with those from 53 healthy adults aged 20-50 years. Amplitudes and peak times of the major components were assessed. There were no significant differences in amplitude or peak time between sexes or between eyes. ERG amplitudes were 25-40% smaller and peak-times were longer in the older compared with the younger age group. In all participants, the bright flash ERG b-wave amplitude had the highest variability; the bright flash ERG a-wave peak time had the lowest. ERGs in a septuagenarian age group show 25-40% lower amplitude than those of a 20 to 50-year-old group and are of longer peak time. With an increasingly ageing population involved in clinical trials, and the potential use of ERG in the assessment both of efficacy and safety in forthcoming therapeutic interventions, it is important that the effects of age are given adequate consideration.

Weeklong improved colour contrasts sensitivity after single 670 nm exposures associated with enhanced mitochondrial function.

Mitochondrial decline in ageing robs cells of ATP. However, animal studies show that long wavelength exposure (650-900 nm) over weeks partially restores ATP and improves function. The likely mechanism is via long wavelengths reducing nanoscopic interfacial water viscosity around ATP rota pumps, improving their efficiency. Recently, repeated 670 nm exposures have been used on the aged human retina, which has high-energy demands and significant mitochondrial and functional decline, to improve vision. We show here that single 3 min 670 nm exposures, at much lower energies than previously used, are sufficient to significantly improve for 1 week cone mediated colour contrast thresholds (detection) in ageing populations (37-70 years) to levels associated with younger subjects. But light needs to be delivered at specific times. In environments with artificial lighting humans are rarely dark-adapted, hence cone function becomes critical. This intervention, demonstrated to improve aged mitochondrial function can be applied to enhance colour vision in old age.

Prospective Study of the Phenotypic and Mutational Spectrum of Ocular Albinism and Oculocutaneous Albinism.

Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky-Pudlak syndrome and Chédiak-Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, GPR143. We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2-186), and eight adults with a median age of 33 years (range 17-39); 52.3% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

Optically Improved Mitochondrial Function Redeems Aged Human Visual Decline.

The age spectrum of human populations is shifting toward the older with larger proportions suffering physical decline. Mitochondria influence the pace of aging as the energy they provide for cellular function in the form of adenosine triphosphate (ATP) declines with age. Mitochondrial density is greatest in photoreceptors, particularly cones that have high energy demands and mediate color vision. Hence, the retina ages faster than other organs, with a 70% ATP reduction over life and a significant decline in photoreceptor function. Mitochondria have specific light absorbance characteristics influencing their performance. Longer wavelengths spanning 650->1,000 nm improve mitochondrial complex activity, membrane potential, and ATP production. Here, we use 670-nm light to improve photoreceptor performance and measure this psychophysically in those aged 28-72 years. Rod and cone performance declined significantly after approximately 40 years of age. 670-nm light had no impact in younger individuals, but in those around 40 years and older, significant improvements were obtained in color contrast sensitivity for the blue visual axis (tritan) known to display mitochondrial vulnerability. The red visual axis (protan) improved but not significantly. Rod thresholds also improved significantly in those >40 years. Using specific wavelengths to enhance mitochondrial performance will be significant in moderating the aging process in this metabolically demanding tissue.

Juvenile Batten Disease (CLN3): Detailed Ocular Phenotype, Novel Observations, Delayed Diagnosis, Masquerades, and Prospects for Therapy.

PURPOSE: To characterize the retinal phenotype of juvenile neuronal ceroid lipofuscinosis (JNCL), highlight delayed and mistaken diagnosis, and propose an algorithm for early identification. DESIGN: Retrospective case series. PARTICIPANTS: Eight children (5 female) with JNCL. METHODS: Review of clinical notes, retinal imaging including fundus autofluorescence and OCT, electroretinography (ERG), and both microscopy and molecular genetic testing. MAIN OUTCOME MEASUREMENTS: Demographic data, signs and symptoms, visual acuity (VA), fundus autofluorescence and OCT findings, ERG phenotype, and microscopy/molecular genetics. RESULTS: Participants presented with rapid bilateral vision loss over 1 to 18 months, with mean VA deteriorating from 0.44 logarithm of the minimum angle of resolution (logMAR) (range, 0.20-1.78 logMAR) at baseline to 1.34 logMAR (0.30 logMAR - light perception) at last follow-up. Age of onset ranged from 3 to 7 years (mean, 5.3 years). The age at diagnosis of JNCL ranged from 7 to 10 years (mean, 8.3 years). Six children displayed eccentric fixation, and 6 children had cognitive or neurologic signs at the time of diagnosis (75%). Seven patients had bilateral bull's-eye maculopathy at presentation. Coats-like exudative vasculopathy, not previously reported in JNCL, was observed in 1 patient. OCT imaging revealed near complete loss of outer retinal layers and marked atrophy of the nerve fiber and ganglion cell layers at the central macula. An electronegative ERG was present in 4 patients (50%), but with additional a-wave reduction, there was an undetectable ERG in the remaining 4 patients. Blood film microscopy revealed vacuolated lymphocytes, and electron microscopy showed lysosomal (fingerprint) inclusions in all 8 patients. CONCLUSIONS: In a young child with bilateral rapidly progressive vision loss and macular disturbance, blood film microscopy to detect vacuolated lymphocytes is a rapid, readily accessible, and sensitive screening test for JNCL. Early suspicion of JNCL can be aided by detailed directed history and high-resolution retinal imaging, with subsequent targeted microscopy/genetic testing. Early diagnosis is critical to ensure appropriate management, counseling, support, and social care for children and their families. Furthermore, although potential therapies for this group of disorders are in early-phase clinical trial, realistic expectations are that successful intervention will be most effective when initiated at the earliest stage of disease.

Deficits in local and global motion perception arising from abnormal eye movements.

Albino mammals exhibit a range of visual deficits including disrupted hemispheric pathways, an underdeveloped central retina, and nystagmus. Recently, it has been reported that albino animals also show deficits in the processing of visual motion, exhibiting higher motion coherence thresholds (MCTs; the proportion of coherently moving elements within a field of randomly moving distracters required to reliably report direction). Here we compare MCTs-collected from human observers with albinism-with an equivalent noise analysis of their fine-direction discrimination and report that their loss in motion sensitivity operates at both the level of local motion processing (of small objects) and at the later stage of global motion pooling. We also compare results from observers with aniridia (characterized by underdeveloped central retina and nystagmus but normal hemispheric visual pathways) and a rare group of observers with albinism who show no nystagmus. For the observers tested, nystagmus proved to be a common feature of individuals showing elevated MCTs. Since it is likely that motion perception is influenced by environmental factors early in development we postulate that the effect of congenital nystagmus on the temporal structure of the natural visual diet disrupts the ability of motion pathways to form normally.

Isolated rod dysfunction associated with a novel genotype of CNGB1.

PURPOSE: To describe the clinical and electrophysiological features of an unusual retinopathy in a patient with a novel genotype of CNGB1, mutations in which are implicated in autosomal recessive retinitis pigmentosa (rod-cone dystrophy). OBSERVATIONS: A 61-year old asymptomatic woman was referred to the inherited retinal disorders clinic because of peripheral retinal pigmentary changes. She had normal visual acuity and color vision. Clinical examination and detailed imaging of the macula were normal, but there was atrophy of the outer retina in the periphery with sparse intra-retinal pigmentation. Electroretinography (ERG) revealed undetectable rod responses, with normal cone-mediated responses. The pattern ERG was normal. Genetic analysis identified two previously unreported variants in CNGB1: (c.2258T > A, p.[Leu753*] and c.807G > C, p.[Gln269His]), shown to be in trans. CONCLUSIONS AND IMPORTANCE: This report describes a functionally cone-isolated retina in an adult, apparently hemizygous for a novel missense mutation in CNGB1, a novel phenotype for this gene. The p.[Gln269His] allele is the first missense change, within the glutamic acid-rich protein (GARP) domain of CNGB1, to be associated with retinal disease in humans.

The fovea regulates symmetrical development of the visual cortex.

The foveal region contains the highest cell density in the human retina; consequently a disproportionately large area of the visual cortex is dedicated to its representation. In aniridia and albinism the fovea does not develop, and the corresponding cortical representation shows a reduction in gray matter volume. In albinos there are chiasmatic irregularities in the hemispheric projections, which are not found in aniridics. Here, we ask whether the anomalies in central retinal development, present in albinism and aniridia, have a wider impact on the architecture of the visual cortex. The length, depth, and topology of the calcarine fissure is analyzed in albino, aniridic, and normal subjects. These measures are compared between groups and between the cortical hemispheres within each subject. We show that the calcarine fissure, where the primary visual cortex is represented, is abnormally short in those lacking a fovea. Moreover, surface reconstructions of the calcarine fissure revealed marked interhemispheric asymmetries. The two groups could not be distinguished on the basis of their cortical features, and we therefore interpret the abnormalities in cortical architecture in terms of the absence of the fovea, the common retinal feature found in both groups.

Phenotypic variation in enhanced S-cone syndrome.

PURPOSE: To characterize the clinical, psychophysical, and electrophysiological phenotype of 19 patients with enhanced S-cone syndrome (ESCS) and relate the phenotype to the underlying genetic mutation. METHODS: Patients underwent ophthalmic examination and functional testing including pattern ERG, full-field ERG, and long-duration and short-wavelength stimulation. Further tests were performed in some patients, including color contrast sensitivity (CCS), multifocal ERG, fundus autofluorescence imaging (FAI), optical coherence tomography (OCT), and fundus fluorescein angiography (FFA). Mutational screening of NR2E3 was undertaken in 13 patients. RESULTS: The fundus appearance was variable, from normal to typical nummular pigment clumping at the level of the retinal pigment epithelium in older patients. Nine patients had foveal schisis, and one had peripheral schisis. Pattern ERG was abnormal in all patients. In all patients, ISCEV Standard photopic and scotopic responses had a similar waveform, the rod-specific-ERG was undetectable and the 30-Hz flicker ERG was markedly delayed with an amplitude lower than the photopic a-wave. Most ERG responses arose from short-wavelength-sensitive mechanisms, and a majority of patients showed possible OFF-related activity. Multifocal ERG showed relative preservation of central function, but reduced responses with increased eccentricity. Mutations were identified in NR2E3 in 12 of 13 patients including four novel variants. CONCLUSIONS: The phenotype in ESCS is variable, both in fundus appearance and in the severity of the electrophysiological abnormalities. The ERGs are dominated by short-wavelength-sensitive mechanisms. The presence, in most of the patients, of possible OFF-related ERG activity is a finding not usually associated with S-cones.

Unilateral Pigmented Paravenous Retinochoroidal Atrophy Associated With Presumed Ocular Tuberculosis.

This report describes a case of unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) in a patient with low-grade unilateral intermediate uveitis. A 31-year-old woman, previously diagnosed with intermediate uveitis in the right eye (OD) presented to the clinic. Best-corrected visual acuity was 20/20 OD. Fundus examination, fluorescein angiography, autofluorescence, and optical coherence tomography OD were in keeping with a phenotypic diagnosis of PPRCA. Electrophysiology showed severe photoreceptor dysfunction of both the rod and the cone systems OD. Systemic workup revealed QuantiFERON-gold positive. This is the first report of unilateral PPRCA secondary to presumed ocular tuberculosis. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:345-349.].