Case Report: Long-term Structural and Functional Effects of Ethambutol Optic Neuropathy.

SIGNIFICANCE: This case report demonstrates reduction in the retinal nerve fiber layer (RNFL) thickness and an abnormal electroretinogram after toxic optic neuropathy from ethambutol, more than 1 year after improvements in visual acuity (VA) and visual fields (VFs) were seen. Although many studies have described complications of ethambutol, continuing reduction in RNFL thickness 2 years after discontinuation has not been described elsewhere. PURPOSE: It is well known that ethambutol can cause optic nerve toxicity, visual impairment, and VF loss. Visual acuity can be regained after stopping the drug; however, the amount and time frame are variable. There are few data on long-term follow-up of these cases to direct clinicians how to proceed once VA has stabilized. Here we present a case with 2 years of follow-up for a patient with ethambutol toxicity, showing the condition change even after VA becomes normal. CASE REPORT: A 61-year-old man presented shortly after discontinuing ethambutol for Mycobacterium avium complex. Visual acuity values were 20/70 in the right eye and 20/125 in the left eye with cecocentral VF scotomas. Optical coherence tomography showed normal RNFL. Visual-evoked potentials were significantly reduced and delayed. Over the course of 2 years, the patient became asymptomatic as VA and VF returned to normal and visual-evoked potential improved. However, the optical coherence tomography RNFL was reduced from each visit to the next, and the electroretinogram showed decreased scotopic and photopic amplitudes. CONCLUSIONS: Signs of ethambutol toxicity may remain or worsen years after discontinuation, even in the absence of patient symptoms and with normal VA and VF.

SEQUENTIAL CHANGES IN HYDROXYCHLOROQUINE RETINOPATHY UP TO 20 YEARS AFTER STOPPING THE DRUG: Implications for Mild Versus Severe Toxicity.

PURPOSE: To characterize the stability or progression of different stages of hydroxychloroquine (HCQ) retinopathy up to 20 years after stopping the drug. METHODS: We reviewed findings from 13 patients with initial HCQ retinopathy classified as early (patchy photoreceptor damage), moderate (ring of photoreceptor thinning or scotoma), or severe (retinal pigment epithelial [RPE] damage). Patients had been off HCQ for as many as 14 years at initial examination and were subsequently followed for 5 years to 8 years with repeated fundus autofluorescence and spectral domain optical coherence tomography. RESULTS: Early and moderate cases stabilized in fundus autofluorescence appearance, foveal thickness, ellipsoid zone line length, and visual acuity for up to 9 years after stopping HCQ. By contrast, severe cases demonstrated a continual loss of these parameters for up to 20 years off the drug. The presence of RPE damage at initial examination predicted progressive retinopathy over many years. CONCLUSION: The steady progression of severe HCQ retinopathy in eyes showing RPE damage after drug cessation suggests a metabolic insult that chronically destabilizes rather than destroys cellular function, with a clinical course resembling that of genetic dystrophies. Our findings stress the importance of early detection to minimize progression and visual loss.

Case Report: Hydroxychloroquine Retinopathy.

SIGNIFICANCE: Hydroxychloroquine retinopathy causes irreversible central visual loss and can progress despite medication discontinuation. Appropriate dosing and recognition of early disease are important to minimize adverse visual sequelae. In 2016, the American Academy of Ophthalmology updated its 2011 recommendations for dosing, screening, and monitoring of hydroxychloroquine retinopathy. PURPOSE: The aim of this study was to report a case of hydroxychloroquine retinopathy in a patient who developed toxicity on a dose meeting safety thresholds from the 2011 guidelines (i.e., 6.5 mg/kg ideal body weight and cumulative dose <1000 g), but exceeding that from the 2016 revised recommendations (i.e., 5.0 mg/kg real body weight). CASE REPORT: A 61-year-old woman with rheumatoid arthritis treated with 400 mg/kg hydroxychloroquine daily for 6 years (daily dose, 5.72 mg/real body weight or 6.5 mg/kg ideal body weight; cumulative dose, 876 g) experienced progressive central vision loss and a scotoma affecting her reading ability and was referred to the Retina service. Prior yearly examination with only Ishihara color vision and Amsler grid testing was normal. On examination, visual acuity was 20/40 in the right eye and 20/30 in the left eye. A fundus examination showed bilateral bull's-eye maculopathy, a classic finding of hydroxychloroquine retinal toxicity. Fundus autofluorescence showed a parafoveal ring of speckled hypoautofluorescence and an external ring of increased signal. There were characteristic structural changes on spectral domain-optical coherence tomography, including parafoveal loss of the ellipsoid zone and outer nuclear layer. Humphrey visual field testing of the central 10-2 revealed incomplete paracentral annular scotoma. Subsequently, hydroxychloroquine was switched to sulfasalazine. CONCLUSIONS: The 2016 American Academy of Ophthalmology guidelines for hydroxychloroquine retinopathy were revised to reflect new dosing and care guidelines for early detection of retinal toxicity and to minimize the extent of irreversible vision loss.

Central scotoma in tobacco-alcohol toxic optic neuropathy measured with semi-automated kinetic perimetry.

PURPOSE: To measure the area of central scotoma obtained with semi-automated kinetic perimetry (SKP) in patients suffering from tobacco-alcohol toxic neuropathy (TATN). METHODS: Twelve eyes of six patients with TATN were examined with SKP. Area of central scotoma was measured in square degrees (deg2). Additionally, static automated perimetry (SAP) within 60° was performed in each patient. RESULTS: Area of central scotoma was 41.8 deg2 for III4e isopter, 22.9 deg2 for I4e isopter and 16.1 deg2 for I2e isopter in TATN patients. SAP revealed central scotoma in all patients. There was 100% of accordance between two methods. CONCLUSION: SKP is comparable with SAP in assessing central scotoma. SKP offers advantage of measuring central scotoma and assessing remaining peripheral visual field in TATN, even with low incidence and prevalence of this clinical entity.

Perifoveal interdigitation zone loss in hydroxychloroquine toxicity leads to subclinical bull's eye lesion appearance on near-infrared reflectance imaging.

PURPOSE: To characterize the ultrastructural and functional correlates of hydroxychloroquine (HCQ)-induced subclinical bull's eye lesion seen on near-infrared reflectance (NIR) imaging. METHODS: An asymptomatic 54-year-old male taking HCQ presented with paracentral ring-like scotoma, abnormal multifocal electroretinography (mfERG) and preserved ellipsoid zone on optical coherence tomography (OCT). Dense raster OCT was performed to create en face reflectivity maps of the interdigitation zone. Macular Integrity Assessment (MAIA) microperimetry and mfERG findings were compared with NIR imaging, en face OCT, retinal thickness profiles and wave-guiding cone density maps derived from flood-illumination adaptive optics (AO) retinal photography. RESULTS: The bull's eye lesion is an oval annular zone of increased reflectivity on NIR with an outer diameter of 1450 µm. This region corresponds exactly to an area of preserved interdigitation zone reflectivity in en face OCT images and of normal cone density on AO imaging. Immediately surrounding the bull's eye lesion is an annular zone (3°-12° eccentricity) of depressed retinal sensitivity on MAIA and reduced amplitude density on mfERG. Wave-guiding cone density at 2° temporal was 25,400 per mm2. This declined rapidly to 12,900 and 1200 per mm2 at 3° and 4°. CONCLUSION: Multimodal imaging illustrated pathology in the area surrounding the NIR bull's eye, characterized by reduced reflectance, wave-guiding cone density and retinal function. Further studies are required to investigate whether the bull's eye on NIR imaging and en face OCT is prominent or consistent enough for diagnostic use.

A Case of Serious Eye Injury Caused by a Mistaken Injection of Methylrosaniline Chloride During Vitreous Surgery.

This case involved a 75-year-old female with left-eye epiretinal membrane (ERM) and cataract who developed serious eye disorders during vitreous surgery due to methylrosaniline chloride (MRC) being mistakenly injected and applied to the retina instead of Brilliant Blue G during internal limiting membrane staining. Once realized, MRC was washed out with intraocular infusion solution, and ERM surgery was successfully completed. Postoperatively, a Descemet's fold and corneal edema, marked reduction in corneal endothelial cell density, and inner retina damage and visual field defect extending from the macula toward the temporal side were observed. MRC was found highly toxic to eye tissues. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:1010-1015.].

We cannot see what she cannot ignore.

A 32-year-old woman presented with the acute onset of a small scotoma in the right visual field. She was initially thought to have optic neuritis, but brain magnetic resonance imaging was normal. A review of her symptoms and medications disclosed recent use of oral contraceptives. Near-infrared imaging was the only objective abnormality, consistent with her Amsler grid changes, leading to the diagnosis of acute macular neuroretinopathy.

RITONAVIR-ASSOCIATED TOXICITY MIMICKING RETINITIS PIGMENTOSA IN AN HIV-INFECTED PATIENT ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY.

PURPOSE: To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. METHODS: Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. RESULTS: 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. CONCLUSION: Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy-associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

ACUTE MACULAR NEURORETINOPATHY AFTER RANIBIZUMAB INJECTION IN A DIABETIC PATIENT.

PURPOSE: To report a case of acute macular neuroretinopathy occurring after intravitreal ranibizumab injection for diabetic macular edema. METHODS: Observational clinical case report. RESULTS: The patient received an intravitreal ranibizumab (0.3 mg) injection for diabetic macular edema. Three days later, he had a decline in vision associated with a central and paracentral scotoma. Optical coherence tomography (OCT) demonstrated bandlike hyperreflectivity of the outer nuclear and plexiform layers corresponding to the patient's scotoma, consistent with the diagnosis of acute macular neuroretinopathy. There was spontaneous resolution of the abnormalities observed in optical coherence tomography, but only partial resolution of the scotoma was observed 4 months after presentation. CONCLUSION: Diabetic retinopathy may be associated with acute macular neuroretinopathy. The temporal relationship between ranibizumab injection and the onset of acute macular neuroretinopathy in this case report raises the possibility of a causal relationship.

Retinal toxicity of high-dose hydroxychloroquine in patients with chronic graft-versus-host disease.

OBJECTIVE: To evaluate retinal toxicity in patients treated with high-dose hydroxychloroquine (HCQ) (Plaquenil, Sanofi Pharmaceuticals) for chronic graft-versus-host disease (GVHD). DESIGN: Cohort study. PARTICIPANTS: Twelve patients with chronic GVHD treated with 800 mg/day HCQ between June 2005 and December 2010. METHODS: Patients in this study underwent ophthalmologic examination yearly and ancillary studies including colour vision, Amsler grid, fundus photographs, Humphrey 10-2 automated perimetry, spectral-domain optical coherence tomography (SD-OCT), and multifocal electroretinography (mfERG). Evidence of HCQ toxicity was determined by the presence of scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, and confirmed by at least 1 objective test including SD-OCT or mfERG. RESULTS: Of the 12 patients, 7 were male and 5 were female. Mean age was 49 years. Mean best corrected visual acuity at baseline was 20/25 and remained 20/25 at final follow-up. Median duration of HCQ treatment was 22.8 months. Median adjusted daily dosage was 11.5 mg/kg/day. Seven patients developed vortex keratopathy. No signs of pigmentary retinopathy or bull's-eye maculopathy were found in any of the patients. Three patients developed retinal toxicity with scotomas in the Amsler grid and Humphrey 10-2 automated perimetry, as well as abnormal mfERG. Retinal structure measured by SD-OCT was abnormal in 2 of the 3 patients with retinal toxicity. Colour vision measured by Ishihara plates, as well as by 100 Hue colour test, was abnormal in 2 of the 3 patients with retinal toxicity. CONCLUSIONS: High-dose HCQ in patients with GVHD was associated with higher incidence and earlier development of retinal toxicity.

Spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss.

PURPOSE: To investigate spectral domain optical coherence tomography findings in long-term silicone oil-related visual loss. METHODS: Four symptomatic patients were reviewed 4 years to 9 years after vitrectomy with silicone oil tamponade for macula-on retinal detachment. Three lost vision with oil in situ, with one at the time of oil removal. Eleven control eyes with good vision were included. Patients underwent assessment of best-corrected visual acuity, contrast sensitivity, Farnsworth-Munsell 100 Hue testing, static perimetry, and spectral domain optical coherence tomography imaging of the macula and disk. RESULTS: Long-term best-corrected visual acuity was significantly reduced in affected eyes (range, 0.44-1.02), as was contrast sensitivity (0.75-1.35) and color discrimination (Farnsworth-Munsell-100 Hue score, 151-390). Static perimetry showed a central scotoma in all affected eyes. Optical coherence tomography revealed microcystic macular changes in the inner nuclear layer of all affected eyes associated with severe loss of the papillofoveal retinal nerve fiber layer. In one patient, serial optical coherence tomography images showed development of microcystic macular changes 18 months after oil removal. Control eyes lacked these features, except two asymptomatic eyes that showed microcystic changes on optical coherence tomography with a corresponding paracentral scotoma. CONCLUSION: We have demonstrated microcystic macular changes in the inner nuclear layer of affected eyes, as well as focal severe loss of the papillofoveal projection. These changes share significant morphologic features reported in multiple sclerosis-associated optic neuritis and Leber hereditary optic neuropathy.