Hearing Dysfunction After Treatment With Teprotumumab for Thyroid Eye Disease.

PURPOSE: To characterize the frequency, severity, and resolution of hearing dysfunction in patients treated with teprotumumab for thyroid eye disease (TED). DESIGN: Prospective observational case series. METHODS: Ophthalmic examination and adverse event assessment, including otologic symptoms, were performed at baseline, after infusions 2, 4, and 8, and at 6-month follow-up in consecutive patients who received at least 4 teprotumumab infusions. Laboratory test results were collected at baseline and during treatment. Audiometry, patulous eustachian tube (PET) testing, and otolaryngology evaluation were obtained for patients with new or worsening otologic symptoms, with a subset obtaining baseline and posttreatment testing. RESULTS: Twenty-seven patients were analyzed (24 females, 3 males, average 56.3 years old). Twenty-two patients (81.5%) developed new subjective otologic symptoms, after a mean of 3.8 infusions (SD 1.8). At 39.2-week average follow-up after the last infusion, most patients with tinnitus (100%), ear plugging/fullness (90.9%), and autophony (83.3%) experienced symptom resolution, whereas only 45.5% (5 of 11) of patients with subjective hearing loss/decreased word comprehension experienced resolution. Six patients underwent baseline and posttreatment audiometry, 5 of whom developed teprotumumab-related sensorineural hearing loss (SNHL) and 1 patient also developed PET. Three of the 5 patients with teprotumumab-related SNHL had persistent subjective hearing loss at last follow-up. A prior history of hearing loss was discovered as a risk factor for teprotumumab-related SNHL (P = .008). CONCLUSIONS: Hearing loss is a concerning adverse event of teprotumumab, and its mechanism and reversibility should be further studied. Until risk factors for hearing loss are better understood, we recommend baseline audiometry with PET testing and repeat testing if new otologic symptoms develop. Screening, monitoring, and prevention guidelines are needed.

TOPOGRAPHIC OPTICAL COHERENCE TOMOGRAPHY SEGMENTATION SHOWS LIMITED ELLIPSOID ZONE RECOVERY IN MILD HYDROXYCHLOROQUINE RETINOPATHY.

PURPOSE: Optical coherence tomography (OCT) cross-sections have shown limited ellipsoid zone (EZ) improvement in mild hydroxychloroquine (HCQ) retinopathy within a few years after drug cessation. However, the extent, functional significance, and stability of such changes over time remain unclear. METHODS: We created en face EZ maps using automated pixel-by-pixel segmentation for four patients with early-moderate HCQ toxicity followed for 6-8 years after drug cessation. These maps were compared with OCT cross-sections, fundus autofluorescence, and automated 10-2 visual fields. RESULTS: One patient had no EZ line loss; one had stable EZ loss throughout follow-up; two showed 30 to 40% reduction in the area of loss, largely in the first 2 years. This limited recovery mostly occurred in regions where the EZ line was only thinned or fragmented; other similar areas did not improve. Fundus autofluorescence hyperfluorescence and visual fields did not show consistent correlation with topography. CONCLUSION: Anatomic EZ recovery, when present, was restricted to regions of mild damage and did not correlate with fundus autofluorescence or improvement in visual fields. Topographic mapping seemed no more sensitive locally than cross-sectional OCT but may aid detection and longitudinal follow-up of toxicity by showing early damage or changes in the macula that could be missed with individual cross-sections.

Bilateral preretinal hemorrhage associated with Kikuchi-Fujimoto disease.

PURPOSE: To present a case of a patient with human immunodeficiency virus (HIV) disease and Kikuchi-Fujimoto disease (KFD) who presented with a unique pattern of retinopathy. OBSERVATIONS: A 7-year-old Taiwanese girl with HIV disease who was recently diagnosed with KFD had a sudden onset of blurry vision in both eyes one month after her KFD systemic symptoms had relatively resolved. Ophthalmic examination showed decreased visual acuity in both eyes (OU). On fundus examination, she had bilateral preretinal, subhyaloid, and vitreous hemorrhage that was more severe than anemic retinopathy. CONCLUSION: Ocular manifestations in Kikuchi-Fujimoto disease are rare; however, if they occur, presentations may vary. The exact etiology of the disease has remained elusive and controversial. This case is the first report of a patient with HIV disease and KFD presenting with ocular involvement. Furthermore, bilateral preretinal, subhyaloid, and vitreous hemorrhage, which was beyond anemic retinopathy, is an unprecedented manifestation of KFD that has not been previously reported. This case highlights the necessity for clinicians to consider all possible differential diagnoses when evaluating patients with similar findings to identify the best therapeutic approach and avoid unnecessary treatment.

SEQUENTIAL RETINAL THICKNESS ANALYSIS SHOWS HYDROXYCHLOROQUINE DAMAGE BEFORE OTHER SCREENING TECHNIQUES.

PURPOSE: We sought to determine the earliest diagnostic signs of hydroxychloroquine retinopathy up to the point of clinical recognition. METHODS: Retrospective series of 6 patients (5 parafoveal disease; 1 pericentral disease) with at least 3 examinations over 3.5 years or more preceding diagnosis of HCQ retinopathy. Spectral domain optical coherence tomography (sdOCT) cross-sections, fundus autofluorescence (FAF) and visual fields were generated clinically. Stored sdOCT data were re-examined later to generate topographic ellipsoid zone (EZ) maps, minimum intensity (MI) analysis and sequential plots of regional retinal thickness. Retrospective series of six patients (5 parafoveal disease; one pericentral disease) with at least three examinations over 3.5 years or more preceding diagnosis of hydroxychloroquine retinopathy. RESULTS: Spectral domain optical coherence tomography cross-sections and fields showed similar sensitivity; fundus autofluorescence was not helpful. In parafoveal cases, EZ topography and minimum intensity analysis were no more reliable. Sequential thickness plots from four parafoveal cases showed dramatic retinal thinning across the posterior pole beginning 4 years to 5 years before clinical diagnosis, with parafoveal regions thinning even faster. The pericentral case showed thinning only outside the central macula. Peripheral EZ loss was more dramatic with EZ topography than sdOCT cross-sections. CONCLUSION: Sequential retinal thickness plots reveal definitive thinning years before current diagnostic procedures. We hope that OCT manufacturers will develop software to display such measurements. Ellipsoid zone topography was not more sensitive than sdOCT cross-sections, but important for recognizing pericentral disease.

Impending central retinal vein occlusion in patient with idiopathic cutaneous leukocytoclastic vasculitis.

PURPOSE: To report a case of impending central retinal vein occlusion (CRVO) associated with idiopathic cutaneous leukocytoclastic vasculitis (LCV) that demonstrated significant resolution following treatment with intravenous (IV) methylprednisolone. OBSERVATIONS: A 27-year-old man presented to a tertiary Uveitis Clinic with a five-day history of blurry vision in the right eye (OD). He had a history of a purpuric rash and arthralgias five years ago and a biopsy-confirmed diagnosis of LCV controlled with colchicine two years ago in India. Recently, he presented with a recurrent rash and severe abdominal pain. After being evaluated by rheumatology and gastroenterology, he was placed on Helicobacter pylori treatment and high dose oral prednisone, which improved his skin and gastrointestinal symptoms. At the first ophthalmic exam, his systemic findings included lower extremity purpura. His best-corrected visual acuity (BCVA) was 20/20 in both eyes (OU). Slit-lamp examination revealed no cells or flare in OU. Dilated fundus exam showed mild enlarged, tortuous veins, optic nerve hemorrhage, and intraretinal hemorrhages temporal to the macula in OD. Spectral-domain optical coherence tomography (SD-OCT) demonstrated multiple hyper-reflective, plaque-like lesions involving the inner nuclear layer, consistent with paracentral acute middle maculopathy (PAMM). The patient was diagnosed with impending central retinal vein occlusion (CRVO) in OD. Laboratory evaluations were unremarkable. Aspirin was initially started for the patient but was later held due to the worsening of retinal hemorrhage and retinal vein tortuosity at the one-week follow-up. The patient then received three doses of intravenous methylprednisolone, followed by systemic oral prednisone and mycophenolate mofetil. One month later, retinal hemorrhages, venous stasis, and skin manifestations resolved. CONCLUSION AND IMPORTANCE: Ocular involvement in LCV is rare and may present with different manifestations. The index case is the first report of impending CRVO in a patient with idiopathic LCV and without any other known risk factors for CRVO. Our report not only describes the unique course of LCV-related ocular involvement, but also introduces and underscores a potentially effective therapeutic plan.

The rapid N-wave as a potentially useful measure of the photopic negative response.

PURPOSE: The photopic negative response (PhNR) correlates with ganglion cell function and has previously been examined as an indicator of glaucomatous optic nerve damage. However, it is a prolonged response that is measured against baseline, and its clinical utility has been limited by extensive variability, poor repeatability, and baseline instability. We have observed a distinct brief negative wave ("N-wave") commonly present within the slow PhNR trough, which may provide practical and analytic advantages as a clinical measure. METHODS: We reviewed data from an interventional trial of 59 glaucoma patients who had 4 exams over an 8-month period. The PhNR was recorded with standard ISCEV stimuli (1 Hz and in some cases 4 Hz stimulation), and N-waves were measured manually, relative to return to baseline. RESULTS: N-waves, when present, could be measured easily despite shifting baselines and a degree of background noise. The PhNR median amplitude centered around 18 µV, while the N-wave median centered around 7 µV, with a distribution of responses skewed toward low or zero amplitudes. CONCLUSIONS: The N-wave appears to be a component of the longer PhNR, though its exact origin and significance remain unclear. As a rapid waveform that is independent of baseline, the N-wave is in many ways easier to measure accurately than the slower PhNR, which is highly dependent on baseline stability. The N-wave may prove useful clinically if further studies can optimize its stimulation, show its behavior in normal individuals and find correlation with markers of optic nerve disease.

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.

Unilateral retinitis pigmentosa in children.

BACKGROUND: Retinitis pigmentosa (RP) is a group of rare inherited retinal disorders characterized by diffuse progressive degeneration of the retina that typically presents bilaterally. Unilateral RP has not often been reported in children. We present a series of cases that illustrate discrimination between unilateral and asymmetric disease and between dystrophy and acquired degeneration. METHODS: Four patients (9-15 years of age; 3 females) were referred to our institution for possible unilateral RP based on fundus appearance and unilateral symptoms. All underwent full-field electroretinography (ERG), spectral domain optical coherence tomography (SD-OCT), widefield and color fundus photography, and fundus autofluorescence (FAF) imaging. Genetic testing and a vitamin and essential fatty acids panel were also conducted in 1 patient. RESULTS: Unilateral retinal degeneration was confirmed in 2 patients, whose fellow eyes showed no abnormalities on ERG or imaging. The other 2 patients were found to have highly asymmetric retinal degeneration based on ERG, wide-angle images, and repeated examinations (range, 0.3-9.8 years). Genetic testing and blood testing in 1 unilateral case were negative. CONCLUSIONS: Childhood-onset "unilateral RP" remains a difficult and uncertain diagnosis. ERG testing and longitudinal and widefield fundus examination are necessary to exclude asymmetrical disease. Although unilateral degeneration may exist in some children, its inherited or acquired etiology remains poorly understood.